Publication for Ldlr and Srebf2

Species	Symbol	Function*	Entrez Gene ID*	Other ID	Gene coexpression	CoexViewer
mmu	Ldlr	low density lipoprotein receptor	16835			[link]
mmu	Srebf2	sterol regulatory element binding factor 2	20788

Pubmed ID	Priority	Text
30354208	0.99	SREBP2 where it transactivates LDLR and other target genes, primarily via SRE motifs in their promoters.
	0.98	LDLR regulation is at the transcriptional level and controlled by sterol response element binding protein 2 (SREBP2), which itself responds to intracellular cholesterol levels.
	0.98	LDLR expression and impacts plasma LDL-C levels in normolipidemic mice through a molecular mechanism different from other nuclear receptors such as peroxisome proliferator-activated receptors (PPARs), SREBP2 and LXR that regulate LDLR gene expression at transcriptional levels or posttranslational levels.
	0.95	SREBP2 was inhibited, which led to the suppression of LDLR gene expression.
	0.94	Ldlr mRNA levels significantly to 1.7-fold of control, whereas other typical SREBP2-target genes such as Pcsk9 and Hmgcr were unaffected by OCA.
	0.94	LDLR mRNA levels in all tested HPHs, whereas mRNA levels of HMGCR, SREBP1 and SREBP2 were unchanged (Fig. 5A-C).
28178673	0.99	SREBF2 activates PCSK9 and LDLR transcription through binding to functional sterol regulatory elements in the promoters of these genes.
26291618	0.98	Low density lipoprotein receptor (LDLr), the primary receptor in maintenance of the balance of lipid metabolism, is highly expressed in kidney LDLr, sterol-regulatory element-binding protein-2 (SREBP2) and SREBP-cleavage activating protein (SCAP) form a tight feedback loop which forms the pivotal system in regulating absorption of LDL cholesterol.
	0.98	LDLr gene is up- or downregulated, which is mediated by translocation of SREBP2.
	0.98	LDLr, SREBP2 and SCAP in HFD-fed mice was markedly increased, compared with that in normal mice.
	0.98	LDLr-SREBP2-SCAP feedback in HMCs, and Ang-(1-7) exacerbates this feedback system to inhibit accumulation of LDL.
	0.98	LDLr, SREBP2 and SCAP in renal tissues of HFD mice induced cholesterol uptake, which possibly contributed to renal cholesterol accumulation.
	0.97	LDLr, SREBP2 and SCAP, and then, decreased lipid deposition in kidney and improved renal injury.
	0.97	LDLr gene transcription is suppressed when the SREBP2-SCAP complex remains in the ER in a high-cholesterol environment.
	0.97	LDLr-SREBP2-SCAP negative feedback system, subsequently exacerbating lipid accumulation in kidney.
	0.97	LDLr, SREBP2 and SCAP expression.
	0.97	LDLr-SREBP2-SCAP pathway, opposite to the in vitro findings, and Ang-(1-7) improves this regulation.
	0.97	LDLr-SREBP2-SCAP pathway stimulated by LDL in vitro.
	0.97	LDLr-SREBP2-SCAP pathway.
	0.96	low density lipoprotein receptor-sterol regulatory element binding proteins 2-SREBP cleavage activating protein (LDLr-SREBP2-SCAP) system by suppressing inflammation in high fat diet (HFD)-fed mice.
	0.96	LDLr-SREBP2-SCAP feedback system.
	0.96	LDLr, SREBP2 and SCAP expression in kidney.
	0.96	LDLr-SREBP2-SCAP feedback loop critical for maintaining lipid uptake and synthesis is disrupted.
	0.95	LDLr-SREBP2-SCAP pathway, leading to exacerbation of lipid uptake and deposition.
	0.95	LDLr-SREBP2-SCAP pathway.
	0.94	LDLr-SREBP2-SCAP pathway, consequently reducing renal damage induced by lipid.
	0.93	LDLr, SREBP2 and SCAP through its anti-inflammation activity, leading to improvement of proteinuria, blood urea nitrogen, and serum creatinine.
	0.92	LDLr- SREBP2-SCAP pathway.
	0.90	LDLr-SREBP2-SCAP Pathway
	0.89	LDLr-SREBP2-SCAP pathway
	0.66	LDLr, SREBP2 and SCAP in HFD mice in the current study.
31239739	0.98	low density lipoprotein receptor (LDLr) is the mediator of cholesterol uptake, the two key proteins which are predominantly regulated by SREBP-2.
	0.98	LDLr is mediated via a negative feedback mechanism that is tightly controlled by the other two proteins, SREBP-2 and SREBP SCAP, which are important for keeping a balance of cholesterol at cell and systemic level.
	0.98	SREBP2-LDLr negative feedback system is disrupted by damage factors, the increasing HMGCR-mediated cholesterol synthesis and LDLr-mediated cholesterol uptake may exacerbate cholesterol accumulation in kidneys, subsequently causing renal injuries mediated by lipids.
	0.98	LDLr, SREBP2, and SCAP proteins in the renal tissue of db/db mice was significantly down-regulated after treatment with quercetin for 10 weeks, and the differences were statistically significant (P<0.01 or P<0.05, Figure 8B), confirming the down-regulated effect of quercetin on the relative expression of key proteins in the SCAP-SREBP2-LDLr signaling pathway.
	0.97	SREBP2-LDLr signaling pathway.
	0.97	LDLr, SREBP2, and SCAP expression, the renal expression of HMGCR protein was down-regulated with an increasing dose of quercetin in db/db mice as compared with diabetic controls after treatment for 10 weeks, and the differences were statistically significant (P<0.05, Figure 8B).
	0.96	LDLr, HMGCR, SREBP-2, and SCAP subsequently attenuated the renal lipid profile change and lipid droplet accumulation, resulting in the alleviation of renal injury of db/db mice.
	0.96	LDLr, SREBP2, and SCAP, was dramatically higher in diabetic control group compared with non-diabetic control group, and the higher level of corresponding values was significantly down-regulated in diabetic mice after administration for 10 weeks as compared with diabetic controls.
	0.96	SREBP2-LDLr signaling pathway, resulting in the alleviation of DM-associated renal injury.
	0.94	LDLr-SREBP2-SCAP signaling pathway in early stage DN, and the blockade of these pathways slows the progression and development of DN.
	0.93	SREBP2-LDLr signaling pathway and the expression of HMGCR in the kidneys, could be therapeutic mechanisms for ameliorating early stage DN.
	0.92	SREBP2-LDLr signaling pathway.
	0.92	LDLr, SREBP2, and SCAP in renal tissues was dramatically higher in diabetic control group than those in non-diabetic control group after administration for 10 weeks, and the differences were statistically significant (Figure 8A).
	0.91	SREBP2-LDLr signaling pathway.
	0.86	SREBP2-LDLr signaling pathway
	0.83	SREBP2-LDLr signaling pathway in early stage diabetic nephropathy
18852694	0.98	SREBP2 controls expression of LDLR and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis (Brown and Goldstein, 1997; Shimano, 2001).
	0.98	LDLR expression is primarily regulated by the activity of SREBP2, which is dependent on cellular sterol levels.
	0.98	SREBP2 processing and expression of the LDLR (Du et al., 2006).
	0.98	LDLR expression by fenofibrate is sustainable and dependent on the SRE and the activity of SREBP2, the primary transcriptional regulator of LDLR expression.
	0.98	SREBP2 processing from its precursor to a mature form, thereby inhibiting the expression of SREBP2 target genes, including the LDLR (Du et al., 2006).
	0.98	LDLR expression by the activation of Akt and consequently the maturation of SREBP2.
	0.97	LDLR expression is predominantly regulated by sterol regulatory element-binding protein 2 (SREBP2).
	0.97	LDLR expression in mice by a mechanism involving Akt phosphorylation and LDLR gene transcription mediated by SREBP2.
	0.97	LDLR expression and reduced plasma LDL cholesterol levels, and that this process occurred though the activation of SREBP2 and phosphorylation of Akt.
	0.97	LDLR expression, suggesting that fenofibrate may modulate the SREBP2 pathway to activate hepatic LDLR expression.
	0.97	LDLR promoter activity by fenofibrate indicated that fenofibrate may activate SREBP2.
	0.97	SREBP2 and Akt phosphorylation was required for fenofibrate-induced hepatic LDLR expression.
	0.96	LDLR expression by fenofibrate suggests that the activity of SREBP2 is required.
	0.95	LDLR expression by fenofibrate occurs through the activation of SREBP2 and Akt phosphorylation
	0.91	LDLR expression by increasing maturation of SREBP2 and phosphorylation of protein kinase B (Akt) but had no effect on SREBP cleavage-activating protein.
31317882	0.98	SREBP2 binds specifically to the sterol-regulatory element (SRE) on the LDLR promoter, and increases LDLR transcription.
	0.98	SREBP2 also plays an important role in the feedback regulation of LDLR, and mediates intracellular cholesterol homeostasis.
	0.98	SREBP2 in renal mesangial cells and podocytes, leading to increased LDLR transcription and foam cell formation.
	0.98	SREBP2 has a key role in the promotion of LDLR transcription, and the interaction of 3 proteins (SCAP-SREBP2-LDLR) maintains LDLR transcription at a relatively steady state.
	0.98	SREBP2 in renal mesangial cells and podocytes, and this allows the SCAP-SREBP2 complex to escape from the endoplasmic reticulum; SREBP2 then moves into the Golgi for lysis and activation, and this promotes LDLR transcription in mesangial cells and podocytes, and thereby increases the intracellular level of cholesterol.
	0.98	LDLR by upregulating SREBP2 in intrinsic renal cells.
	0.98	LDLR and increasing the expression of SREBP2.
	0.97	sterol regulatory element binding protein 2 (SREBP2) acts as a key transcription factor that regulates LDLR expression.
	0.97	SREBP2, leading to an increase of LDLR transcription and eventually to increased deposition of lipids in the kidney.
	0.67	low-density lipoprotein receptor (LDLR) and its transcriptional activator (sterol regulatory element binding protein-2, SREBP-2) increased.
21703998	0.98	low density lipoprotein receptor (LDLR) via activation of sterol regulatory element binding protein-2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile.
	0.98	LDLR expression is a particular target of SREBP-2, nuclear abundance (activation) of which increased significantly in HF-fed foz/foz mice at 12 weeks (P=0.004, Figure 3A).
	0.98	SREBP-2 and LDLR, and lowering LRH-1 and Bsep expression in hepatocytes.
	0.98	SREBP-2 and LDLR, while simultaneously down-regulating LRH-1 gene expression and Bsep, as observed in vivo.
	0.98	SREBP-2, LRH-1), resulting, respectively, in increased LDLR expression on hepatocytes and profound down-regulation of cholesterol biotransformation and FC/BA efflux pathways in the liver.
	0.97	SREBP-2 expression (P<0.0001, Figure 4A,D) with concomitant induction of LDLR (P<0.0001, Figure 4B,D).
	0.97	SREBP-2 expression, and we confirmed that 48h exposure of primary hepatocytes to the same concentrations of insulin that circulate in these obese, diabetic foz/foz mice induce both SREBP-2 and LDLR, as well as suppressing LRH-1 and Bsep gene expression.
	0.96	SREBP-2 and LDLR and suppression of bile salt export pump.
	0.93	SREBP-2 and LDLR and suppresses LRH-1 and Bsep in primary murine hepatocytes
30863273	0.98	SREBP-2 regulates the transcription of LDLR for cellular uptake of LDL cholesterol and clearance of plasma cholesterol, whereas SREBP-1 seems to be involved in energy metabolism including fatty acid metabolism.
	0.97	SREBP-2, and LDLR was considerably upregulated (P < 0.05) (Fig. 2b), especially in the duodenum and jejunum.
	0.97	SREBP-2 and LDLR in the duodenum and jejunum segments, compared with those fed the HFC diet.
	0.97	SREBP-2 and upregulated the protein expression of LDLR, which increased intestinal cholesterol removal and decreased plasma cholesterol levels.
	0.96	SREBP-2, and LDLR expression in the small intestine tissues of mice fed a HFC diet.
	0.95	SREBP) 2, low-density lipoprotein receptor, adenosine triphosphate (ATP)-binding cassette A1, and ATP-binding cassette G1, while decreasing the protein expression of Niemann-Pick C1-like protein 1, SREBP-1, fatty acid synthase, and acetyl-coenzyme A carboxylase, which were involved in intestinal cholesterol metabolism.
	0.95	SREBP-2, and LDLR in the jejunum (P < 0.05), while only minor changes were observed in the duodenum and ileum.
	0.92	SREBP-2 and then increasing the expression of LDLR in the small intestine tissue of C57BL/6 mice (oat fiber mainly in the duodenum and jejunum; wheat bran fiber only in the jejunum).
	0.86	SREBP-2, and LDLR in small intestine tissue samples by Western blot (Fig. 2a).
23862065	0.98	LDLr expression is classically regulated through sterol regulatory element binding protein 2 (SREBP2), signaled through cellular cholesterol.
	0.98	LDLr mRNA (Figures 3(a) and 4(a), resp.), likely the result of a reduction in hepatic cholesterol (Figure 2(b)) and subsequent induction of nuclear SREBP2 protein abundance (Figure 5(b)).
	0.98	LDLr are transcriptionally upregulated following SREBP2 cleavage at the endoplasmic reticulum and subsequent nuclear translocation.
	0.97	LDLr through SREBP2.
	0.97	SREBP2 expression and LDLr activity.
	0.96	SREBP2, LDLr, and PCSK9.
	0.93	SREBP2 protein (1.8-fold of HF group) and LDLr mRNA (1.4-fold of HF group).
	0.83	LDLr mRNA (1.4-fold of HF control) and nuclear SREBP2 protein (1.8-fold of HF control).
28808191	0.98	SREBP2 to the SRE of the LDLR gene and HMGCR gene promotes transcription of the mRNAs, ultimately resulting in increased LDLR protein on the cell surface and increased HMGCR protein in the ER membrane.
	0.98	LDLR (IDOL) acts as an E3 ubiquitin ligase specific for LDLR and promotes the proteolytic degradation of LDLR[ , - ] independent of SREBP2.
	0.98	SREBP2, which can lead to a confounding effect of low cellular cholesterol levels leading to upregulation of HMGCR, LDLR (increasing cellular cholesterol levels through endogenous and exogenous pathways) and upregulation of PCSK9 (decreasing cell surface levels of LDLR).
	0.98	SREBP2 mechanism is the primary regulator of LDLR levels notwithstanding IDOL's function.
	0.98	SREBP2, thereby preventing upregulation of transcription of LDLR and HMGCR (among others).
	0.97	LDLR, and stimulate the expression of ABCA1/ABCG1 to promote cholesterol removal from the cell, thereby acting as an effective foil to the SREBP2 pathway.
	0.97	SREBP2, and over time, should shut down synthesis of the LDLR as it does in fibroblasts.
	0.97	LDLR expression levels, not SREBP2.
31870234	0.98	LDLR, very-low-density lipoprotein receptor (VLDLR), and SREBP2 in the liver in both UUO and L-NAME models (Figures 2E, 2F, and 3A through 3C).
	0.96	LDLR, VLDLR, and SREBP2 (Figure 5A and 5E).
	0.96	LDLR, VLDLR, and SREBP2 (Figure 7A).
	0.94	LDLR, VLDLR, and SREBP2.
	0.94	LDLR, VLDLR, and SREBP2.
	0.94	LDLR, VLDLR, and SREBP2.
	0.93	low-density lipoprotein receptor, very-low-density lipoprotein receptor, sterol-regulatory element binding protein 2, and fatty acid beta-oxidation-related factors, and ameliorated renal fibrosis-related molecules both in the unilateral ureteral obstruction and N-nitro-l-arginine methyl ester models.
	0.93	LDLR and SREBP2 in liver was increased obviously in the PCSK9Qbeta-003 vaccine group.
31327168	0.98	Srebp2 and target genes involved in cholesterol synthesis, including Hmgcr, Acss2, Pmvk, Mvd, Fdft1, Ldlr, and Sqle (Figure 2A).
	0.98	SREBP2 pathway by elaidate is expected to enhance the extraction of LDL from the bloodstream by activating the transcription of Ldlr.
	0.98	LDLR protein levels, via a mechanism independent of SREBP2 and dependent on SREBP1.
	0.97	LDLR protein levels, which is independent of SREBP2 and dependent on SREBP1 and SCAP.
	0.97	Ldlr mRNA in Hepa1-6 cells, which was mediated by a functional SCAP-SREBP2 pathway.
	0.96	SREBP2 appears to be the primary regulator of LDLR in Hepa1-6 cells.
	0.92	LDLR protein in Hepa1-6 cells treated with Srebp2 siRNA but not Srebp1 or Scap siRNA (Figure 3E).
20227267	0.98	SREBP2, regulates expression of the genes for many of the enzymes of the cholesterol synthesis pathway and the LDL receptor (see below), demonstrating one of the first examples of nutrient regulation of gene expression.
	0.97	SREBP2 always plays a major role in the regulation of expression of the LDL receptor.
	0.96	SREBP2 in regulating LDL receptor expression through direct interaction with an SRE in the promoter of the receptor gene and is supported by the strong correlation seen between SREBP2 and LDL receptor mRNA across all of the diets (Fig. 3a).
	0.95	SREBP2 mRNA remains to be established, but this is again likely to be the cause of the reduction in LDL receptor expression.
	0.95	LDL receptor expression, probably through modulation of activity of SREBP2.
	0.93	SREBP2 and LDL receptor mRNA concentrations.
21459323	0.98	SREBP-2 transcriptional activity, as evidenced by decreased nuclear SREBP-2-induced autoregulation and transcription of the LDLR promoter in response to resveratrol.
	0.98	LDLR-/- mice with the blockade of VLDL/LDL clearance, which is consistent with decreased hepatic SREBP-2 processing and HMGCS and HMGCR expression.
	0.97	SREBP-2-induced transcriptional activation of SRE-containing target genes including 4XSRE-Luc and LDLR-Luc reporter genes, comparable to its effects on SREBP-1c promoter (Fig. S5D-F).
	0.96	SREBP-2 that were a 2.8-fold increase in HFHS-fed LDLR-/- mice, which was accompanied by slight changes in SREBP-2 precursor (Fig. 2A-C).
	0.96	SREBP-2 precursor was present in transfected cells and in normal LDLR-/- mouse livers (Fig. S5A and B).
	0.93	SREBP-2, inhibits expression of their target lipogenic enzymes, and reduces lipid accumulation in the liver of the insulin resistant LDLR-/- mice
22666465	0.98	SREBP-2 complex binds to the SRE on the LDLR promoter to activate its promoter activity and that SREBP-1 also binds to the SRE without complex formation with DJ-1.
	0.98	SREBP-2 complex binds to the SRE on the LDLR promoter to activate its promoter activity and that SREBP-1 also binds to the SRE without complex formation with DJ-1.
	0.97	SREBP-2, but not for SREBP-1, significantly reduced expression levels of LDLR mRNA.
	0.91	SREBP-2 and SREBP-1 do not significantly reduce the expression level of LDLR mRNA in DJ-1-knockdown D2 cells (Figure 6C).
	0.77	SREBP-2 and involvement of DJ-1 in LDLR expression.
27892461	0.98	SREBP2-dependent transcriptional regulation, including Srebf2, Ldlr, Pcsk9 and Hmgr, while a slight increase in Srebf1c expression was observed (Supplementary Fig. 6I).
	0.98	SREBP2- dependent LDL receptor upregulation in response to AMPK-independent suppression of cholesterol synthesis.
	0.97	sterol response element-binding protein-2 (SREBP2)-dependent LDL receptor transcription.
	0.97	Srebf2 and Ldlr expression by >2-fold in both Apoe-/- and DKO mice when compared with their respective HFHC-fed controls (Fig. 3n), an effect that was further supported by an increase in plasma membrane-associated LDLR in liver sections from ETC-1002-treated mice (Fig. 3o).
	0.96	SREBF2, HMGR, PCSK9 and LDLR mRNA, with maximum effects reaching 1.4, 1.3, 1.5 and 2.3-fold, respectively (Fig. 5f).
28244871	0.98	Srebf-2 from hepatocytes and confirmed that SREBP-2 regulates all genes involved in cholesterol biosynthesis, the LDL receptor, and PCSK9; a secreted protein that degrades LDL receptors in the liver.
	0.98	SREBP-2 mediates the regulated expression of cholesterol biosynthetic genes and also controls steady-state tissue cholesterol concentrations by simultaneously regulating cholesterol synthesis and uptake from plasma and by modulating the expression of the LDLR and PCSK9.
	0.96	SREBP-2 in the liver reduced the amount of LDLR mRNA by ~20% but there was an accompanying ~80% reduction in the mRNA level of PCSK9 (Figure 2A).
	0.88	Srebf-2-/- mice, the reduction in LDLR production was balanced by the reduction in PCSK9-mediated LDLR destruction, which ultimately led to no measurable change in steady-state LDLR protein levels (data not shown).
	0.83	LDLR protein level was not reduced in hepatocyte-Srebf-2-/- livers despite a 20% reduction in LDLR mRNA levels; however, the mRNA levels of PCSK9 were reduced by 80% in hepatocyte-Srebf-2-/- livers.
26344763	0.98	LDLR activity are associated with cholesterol depletion from the intracellular membranes, and lead to compensatory cleavage-based activation and nuclear translocation of sterol regulatory element-binding protein 2 - SREBP2 (nSREBP2), which positively regulates genes involved in cholesterol synthesis.
	0.98	LDLR and nuclear SREBP2, while treatment with the EGFR inhibitor erlotinib reduced the expression of these proteins (Fig. 5A, B).
	0.98	SREBP2 and LDLR.
	0.71	SREBP2, and depleted LDLR in A431 cells in vitro (Fig. 5G).
30580099	0.98	SREBP2 pathway could be repressed in the ACSL1 deficient liver leading to reduced LDL receptor (LDLR) expression.
	0.98	SREBP2 target genes in cholesterol biosynthetic pathway including Ldlr, Pcsk9, Hmgcr, Hmgcs1, Pmvk and Acat2 (Fig. 3F).
	0.97	SREBP2 pathway in ACSL1 depleted livers was severely repressed with a 50% reduction of LDL receptor protein levels.
	0.89	LDLR protein levels in Ad-shAcsll transduced mice were 50% (p < 0.01) lower than that in control mice and the amount of mature form of SREBP2 (mSREBP2) in ACSLl-depleted liver was only 47% (p < 0.001) of the control (Fig. 3E).
22992388	0.98	Ldlr, and Srebf2 genes was upregulated in the livers of the P. gingivalis-infected mice compared with the sham-infected mice.
	0.92	LDLR expression is also positively regulated by SREBP2 , upregulation of Ldlr could be an effect of the infection.
	0.86	LDL receptor (LDLR) gene and protein expression, as well as liver X receptors (Lxrs), inducible degrader of the LDLR (Idol), and sterol regulatory element binding transcription factor (Srebf)2 gene expression, were examined in the liver.
23536474	0.98	SREBP2 precursor to the Golgi where two steroid sensitive proteases (S1P and S2P) cleave an N-terminal fragment (68 kDa), subsequently translocating into the nuclei to activate its target genes, including LDL receptor and key genes involved in de novo cholesterol synthesis.
	0.98	SREBP2 and subsequent stimulation of de novo cholesterol synthesis and LDLR-mediated cholesterol uptake to reduce serum cholesterol.
	0.98	SREBP2 induces LDLR-mediated LDL-C uptake into hepatocytes.
24978143	0.98	SREBP2, however, has recently been explored and represents another layer of regulatory control of LDLR gene expression.
	0.98	SREBP2 regulated genes including LDLR, HMGCR and PCSK9 compared with mice injected with a control lentivirus.
	0.98	SREBP2, suggesting a role for this miRNA in also controlling LDL-C through the regulation of the SREBP2-dependent gene, LDLR.
25352833	0.98	LDLR and SREBP-2 expression and suggesting that inflammatory stress may exacerbates progression of fatty liver in NAFLD.
	0.98	SREBP-2, LDLR, and SREBP-1c expression.
	0.97	LDL receptor (LOX-1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), and acyl-CoA carboxylase (ACC) was detected, whereas expression of SREBP-1, SREBP-2, HMGCR, peroxisome proliferator-activated receptor alpha (PPAR-alpha), fatty acid binding protein (L-FABP), and carnitine palmitoyltransferase 1A (CPT1A) was decreased.
26226008	0.98	SREBP2 mRNA and protein expression in vitro, leading to a downstream decrease in SREBP2-responsive genes, including LDL receptor (LDLR), resulting in a subsequent decrease in cellular LDL uptake.
	0.98	SREBP2 and its downstream targets, leading to a reduction in LDLR-mediated cholesterol uptake.
	0.96	SREBP2 upregulates cholesterol synthesis and uptake by increasing HMGCoA-R, HMGCoA-S1, methylsterol monoxygenase (SC4MOL), LDLR, and SRB1, and decreases cholesterol efflux and catabolism by suppressing ABCA1, ABCG1, ABCG5/G8, and CYP7A1.
26445568	0.98	LDLR is transcriptionally regulated by the sterol regulatory element binding protein 2 (SREBP-2).
	0.97	SREBP-2 pathway and increasing the level of the LDLR, which results in decreased de novo cholesterol synthesis and plasma LDL-C levels.
	0.96	LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2 (SREBP-2) and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9 (PCSK9) and inducible degrader of the LDLR (IDOL).
19098903	0.98	SREBP2 transcriptional activity, there was an increase in the expression of other SREBP2 target genes, such as LDLR (data not shown).
	0.98	SREBP2 was confirmed by increased expression of LDLR (data not shown), one of the SREBP2 target genes.
19520913	0.98	LDLR protein levels in MEFs (Fig. 3A) and McR-H7777 cells (Fig. 3B), without affecting LDLR or LXR or SREBP2 target mRNAs (Figs. 3C and S5), suggesting that Idol activity is a physiological mechanism for regulating LDLR abundance.
	0.94	SREBP-2 target genes was not affected by Idol expression (Fig. S7E), but LDLR protein levels were markedly reduced (Fig. 5E).
20015660	0.98	SREBP-2 is transferred to the nucleus and binds to the SRE in the LDL-R gene promoter.
	0.97	LDL-R gene is subject to feedback regulation by SREBP-2.
22540255	0.98	SREBP2 and LXR work in concert to reduce excess cellular cholesterol by controlling uptake (i.e., down-regulation of LDLr expression), synthesis, and efflux.
	0.98	SREBP2 releases the N-terminus, which is a basic helix-loop-helix leucine zipper transcription factor that travels to the nucleus to activate transcription of genes involved in cholesterol biosynthesis and cholesterol uptake (i.e., LDLr).
22962999	0.98	LDLR degradation through PCSK9 mRNA up-regulation in the SREBP2 signaling pathway.
	0.97	LDLR and SR-B1 expression, while fucoxanthin increases the expression of SREBP2, which up-regulates LDLR.
23838163	0.98	SREBP2 along with its intronic microRNA-33 (miR-33), which replenishes cellular cholesterol by inducing genes that encode proteins such as 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase and LDL receptor (LDLR) and suppressing the ATP-binding cassette transporter 1 (ABCA1).
	0.97	SREBP2-targeted genes, ie, HMG-CoA reductase, HMG-CoA synthase, squalene synthase, and LDLR was higher with OS than PS (Figure 1C).
24603306	0.98	Ldlr is controlled by the sterol-responsive element binding protein 2 (Srebp2), while its turnover depends on proprotein convertase subtilisin/kexin type 9 (Pcsk9), a serine protease.
	0.95	Ldlr, Pcsk9, Pparalpha, Ppargamma, Srebp1, and Srebp2 (Figure 3A).
25777360	0.98	SREBP2 thus leading to an increased expression of the LDLr, which is enough to compensate for the increased cholesterol synthesis and levels of circulating PCSK9.
	0.97	SREBP2 and thus upregulating the LDL receptor mediated reuptake of LDL into the liver.
27050512	0.98	Ldlr expression is primarily regulated by SREBP2 in a cholesterol-dependent manner.
	0.97	LDLR protein expression (-64.7%), the precursor and mature SREBP1 were reduced by 49.1% and 53.8%, respectively, whereas the SREBP2 precursor was unaffected (Figure 3A).
27694328	0.98	Srebf2, Hmgcr, Ldlr, and Pcsk9.
	0.97	SREBP-2 target gene Pcsk9 (encodes proprotein convertase subtilisin/kexin type 9, a protein that binds and negatively regulates hepatic LDLR protein levels33) were all significantly higher at baseline in Mmp9 -/- mice than in WT mice (Figure 2).
28262793	0.98	sterol regulatory element binding protein-2 (SREBP-2), upregulation of the LDL receptor and enhanced cholesterol uptake in the presence of serum.
	0.98	SREBP-2's transcriptionally active fragment then induces the expression of genes such as the LDL receptor and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, with the aim of compensating cellular cholesterol shortage.
28395113	0.98	SREBP-2 target genes (HMGCR, HMGCS, and LDLR) but also ameliorated SREBP-2 gene expression at low cholesterol levels (Fig. 8B).
	0.95	SREBP-2 target genes HMGCR and LDLR.
28427397	0.98	SREBP-2 promotes the expression of target genes involved in cholesterol biosynthesis such as 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS), HMGCR and LDLR.
	0.95	SREBP-2, HMGCR, LPL, and apoB and increased that of LXR in the liver tissue of HCD-fed LDLR-/- mice.
29183708	0.98	SREBP-2 translocates to the nucleus, where it binds to sterol response elements (SREs) present in the promoters of sterol-responsive genes, including HMGCR and the low-density lipoprotein receptor (LDLR), thus promoting cholesterol biosynthesis and uptake.
	0.98	SREBP2- mediated transcription of cholesterol biosynthetic enzymes and LDLR.
32111832	0.98	SREBP2 is primarily implicated in the regulation of genes linked to cholesterol synthesis and uptake, including those encoding for the rate-limiting enzymes in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and squalene epoxidase (SQLE), and the low-density lipoprotein receptor (LDLR).
	0.98	Srebf2 and a panel of its downstream transcriptional targets Hmgcs, Hmgcr, Sqs, Dhcr24, Pcsk9, and Ldlr (Fig. 4c).
18782462	0.98	SREBP-2 is a primary regulator of LDLr gene expression and that SREBP1c may be a target for programming by maternal protein restriction.
19691840	0.98	Srebp2 and LDL receptor were down-regulated as a result of high liver cholesterol.
21810484	0.98	sterol-responsive element binding protein-2 (SREBP-2), which is itself transcribed and activated by proteolytic cleavage upon sterol deprivation to its transcriptionally-active form that binds and activates the sterol responsive elements in the SREBP2 and LDLR promoters.
22848640	0.98	SREBP2, which in turn stimulates the expression of the LDLR resulting in increased LDLc uptake by hepatocytes, and lowering its circulating levels.
23528177	0.98	SREBP-2 from accumulating in nuclei and inducing the expression of genes involved in cholesterol synthesis and transport, e.g., HMG-CoA reductase and low-density lipoprotein (LDL) receptor.
24506864	0.98	SREBP2, the key regulatory enzyme of C biosynthesis, was significantly higher in nuclear extracts from Ldlr-/-/Lrp6mut/mut compared to Ldlr-/- mice (Figure 5D).
25188917	0.98	SREBP2(N)] translocates into the nucleus to serve as a transcription factor for genes involved in de novo synthesis and uptake of lipids and cholesterol, such as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and LDLR.
25550450	0.98	SREBP2 was associated with induction of SREBP2 transactivation targets such as LDLR and squalene synthase (Figure 1B).
26619823	0.98	Ldlr-/- mice in response to activation of both LXR and FXR pathways and suppression of SREBP-2.
26828754	0.98	SREBP2 targets, HMGCR is the rate-limiting step in cholesterol synthesis, and the low-density lipoprotein receptor (LDLR) is the primary mechanism for uptake of extracellular cholesterol.
27211556	0.98	Srebf2, Hmgcr, Hmgcs and Ldlr were decreased by irisin treatment in the presence or absence of OA in cultured hepatocytes (Fig. 4b).
28301372	0.98	LDLR, which is mediated by the transcription factor sterol regulatory element binding protein 2 (SREBP2).
32058941	0.98	SREBP2 pathway by inhibiting HMG-CoA reductase and subsequently activating the expression of LDLR, have also been proven to stimulate PCSK9 gene expression, thus diminish the beneficial effects of statin treatment.
27834848	0.97	SREBP2, and LDLR.
	0.96	SREBP2, low-density lipoprotein receptor (LDLR), and hydroxymethylglutaryl-coenzyme A reductase (HMGR) genes compared with OLZ alone.
	0.95	SREBP2, and LDLR.
	0.94	SREBP2, low-density lipoprotein receptor (LDLR) and hydroxymethylglutaryl coenzyme A reductase (HMGR)).
	0.94	SREBP2 and LDLR compared with the group treated with OLZ alone (73.05% +- 11.82%, p < 0.001, 59.46% +- 9.91%, p < 0.01) (Figure 3B,D,E).
	0.91	SREBP2, and LDLR by 57.71% +- 9.42%, 73.05% +- 11.82%, and 59.46% +- 9.91%, respectively.
	0.90	SREBP2 (94.27% +- 9.62%, p < 0.001) and LDLR (31.03% +- 0.94%, p < 0.05).
	0.84	SREBP2 and LDLR compared with the controls (35.2% +- 10.49%, 28.47% +- 9.03%, both p < 0.05).
28970592	0.97	sterol-regulatory element-binding protein-2 (SREBP-2), hepatocyte nuclear factor 1alpha (HNF-1alpha), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in LDLR+/- mice.
	0.97	sterol-regulatory element-binding protein-2 (SREBP-2), hepatocyte nuclear factor 1alpha (HNF-1alpha), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in LDLR+/- mice.
	0.94	SREBP-2, that is indirectly up-regulated by statin, activates the Ldlr and Pcsk9 genes.
	0.84	SREBP-2, which activates the Ldlr and Pcsk9 genes, and thus makes statin somewhat self-limiting to further reduce LDL-C. To assess the effect of PCSK9Qbeta-003 vaccine on lipid homeostasis in LDLR+/- mice, we evaluated the mRNA expression of SREBP-2, HNF-1alpha and HMG-CoA reductase in liver.
19260826	0.97	Ldlr, two preferential SREBP-2 target genes, was suppressed by desmosterol.
	0.95	SREBP-2 processing (Figure 4A) and decreased Hmgcr, Ldlr and Insig1 mRNA levels (Figure 4B), although less potently than 25HC.
	0.94	SREBP-2 processing as well as Hmgcr, Ldlr and Insig1 expression (Supplementary Figure S2).
26311497	0.97	LDLR, FDPS, SS, ACC, FAS, SCD-1 and GPAT, but also ameliorated gene expression in SREBP pathway, including SREBP-1a, SREBP-1c, SREBP-2 and Insig-1,without change in Scap expression (Fig. 6b).
	0.90	LDLR, FDPS (farnesyl diphosphate synthase), SS, FAS (FA synthase), SCD-1 (stearoyl CoA desaturase-1), ACC (acetyl CoA carboxylase), ACLY (ATP citrate lyase), GPAT (glycerol-3-phosphate acyltransferase), SREBP-1c, SREBP-2, and Insig-1 were all lower in PAQR3-shRNA group than in the control mice.
22441164	0.97	SREBP-2 and its target genes HMG-CoA synthase 1 (HMGCS1), HMGCR, FPPS, IDI1, SQS, squalene epoxidase (SQLE), lanosterol synthase (LSS), 7-dehydrocholesterol reductase (DHCR7), LDL receptor (LDLR) and Insig-1 were all significantly increased 1.6- to 4.7-fold in P0 129 Pex2-/- versus control mouse liver.
23690465	0.97	LDL receptor (LDLR) levels via sterol regulatory element binding protein 2 (SREBP-2) activation .
29091769	0.97	Ldlr-/- and DKO mice may be due to the repression of SREBP-2 and miR-33 under hyperlipidemic conditions.
30443213	0.97	sterol regulatory element-binding protein-2 (SREBP-2), which upregulates the hepatic expression of LDLR, resulting in enhanced LDL-C clearance from circulation.
24364887	0.96	SREBP2, LXR, LDLR, and HMG-CoA. In liver tissue, the mRNA expression of SREBP, LXR, LDLR, and HMG-CoA was clearly lower in the STSST-treated groups than in the HC group (Figure 5).
	0.95	SREBP-2, liver X receptor (LXR), low-density lipoprotein receptor (LDLR), and 3-hydroxy-3methylglutary-CoA (HMG-CoA) was also suppressed in SHSST-treated groups in the liver.
	0.95	SREBP-2, LXR, LDLR, and HMG-CoA. In particular, members of the SREBP family such as SREBP1a, SREBP1c, and SREBP2 are key transcription factors that are known to control the production of lipids for export into the bile as micelles and into the serum as lipoproteins.
	0.94	SREBP-2, LXR, LDLR, and HMG-CoA that govern cholesterol metabolism, and it also suppressed the mRNA expression of TNF-alpha, IL-6, VCAM-1, ICAM-1, and fibronectin in aorta tissue, relative to that in the HC group.
	0.90	SREBP-2, LXR, LDLR, and HMG-CoA. Our results also suggest that SHSST may suppress the initiation of atherosclerosis.
30582457	0.96	Ldlr, Pcsk9, Hmgcr or Srebf2 (Figure 6D-F).
	0.74	Ldlr, Hnf1a, and Srebf2 mRNA levels (Online Figure IV).
22952870	0.96	low density lipoprotein receptor (LDLR), sterol regulatory element-binding protein-1 (SREBP-1), sterol regulatory element-binding protein-2 (SREBP-2), SREBP-cleavage activating protein (SCAP), insulin-induced gene-1 (INSIG-1), site-1 protease (S1P), and site-1 protease (S2P).
24950000	0.95	LDLR, PCSK9 and other four SREBP target genes in all liver samples revealed that mRNA levels of SREBP2-target genes were reduced in the range of 20-40% in ANA group as compared to vehicle group (Fig. 7D), which were corroborative to the results of protein analyses.
	0.92	SREBP2 and LDLR protein levels in liver tissue and decreased serum PCSK9 levels in dyslipidemic mice
	0.67	SREBP2 and LDLR protein levels in liver tissue and elevation of serum cholesterol in dyslipidemic mice treated with ANA
25849138	0.95	SREBP-2 was sufficient to induce Ldlr, Hmgcr and miR-182 (Fig. 2m,n).
	0.94	Srebp-2 and its targets, Hmgcr, Ldlr and miR-182 (Supplementary Fig. 2k).
22225954	0.95	SREBP-2 both in C57BL/6 mice and LDLR-/- mice fed with HCD or HFD.
24158514	0.91	SREBP2 target genes (HMGCR, PCSK9) in mouse primary hepatocytes were not affected by Ad-shHNRNPD infection (Figure 5C), thus confirming the specific targeting effect of the shRNA to hnRNP D. The reduction of hnRNP D by Ad-shHNRNPD transduction with a consequential increase in LDLR protein level was also observed in mouse hepatoma-derived cells (Figure 5D).
18771980	0.89	SREBP-2, HMGCR and LDLR, and to study the correlations between the expression of these mediators.
29904174	0.89	LDLR is SREBP2.
21810592	0.61	SREBP2, FOXO1, ChREBP, PPARalpha, CPT1, and FASN in the livers of diabetic E3LDLR-/- and diabetic E4LDLR-/- mice.