Orphan nuclear receptor small heterodimer partner inhibits angiotensin II-stimulated PAI-1 expression in vascular smooth muscle cells

Lee, Kyeong Min; Seo, Hye Young; Kim, Mi Kyung; Min, Ae Kyung; Ryu, Seong Yeol; Kim, Yoon Nyun; Park, Young Joo; Choi, Hueng Sik; Lee, Ki Up; Park, Wan Ju; Park, Keun Gyu; Lee, In Kyu

doi:10.3858/emm.2010.42.1.002

Cited by 5 publications

(4 citation statements)

References 37 publications

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“…Here, we have to note that insulin rapidly and strongly induced SHP mRNA in both human cells and mice. SHP is an interesting and powerful negative regulator of various nuclear receptors in vivo and in vitro because it lacks the DNA binding domain (Lee et al, 2010). SHP directly binds to FOXO1 or HNF-4α to dissociate them from promoters of G6Pase or PEPCK, respectively (Yamagata et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Insulin-dependent suppression of cholesterol 7α-hydroxlase is a possible link between glucose and cholesterol metabolisms

Park

Pak

2011

Exp Mol Med

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Abbreviations: CDCA, chenodeoxycholic acid; CYP7A1, cholesterol 7α-hydroxylase; FOXO1, forkhead transcription factor O1; FOXO1-3A, constitutively active form of FOXO1; FTF, alpha(1)-fetoprotein transcription factor; HNF-4α, hepatocyte nuclear factor-4α; IRE, insulin-response elements; PGC-1α, peroxisome proliferator activated receptor γ coactivator-1α; SHP, small heterodimer partner AbstractCholesterol 7α-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and metabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulinAkt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activities in a dose-dependent manner. Similarly to bile acids, insulin treatment increased small heterodimer partner (SHP) mRNA rapidly and transiently, leading to the suppression of CYP7A1 transcription in both human and rodents. Chromatin immunoprecipitation showed that FOXO1 directly bound to rat CYP1A1 promoter in the absence of insulin. FOXO1 binding to the rat promoter was diminished by insulin treatment as well as by expression of SHP. Our results suggest that the stimulation of insulin-signaling pathway of Akt-FOXO1 and SHP expression may regulate cholesterol/bile acid metabolisms in liver, linking carbohydrate and cholesterol metabolic pathways. A prolonged exposure of insulin in hyperinsulinemic insulin resistance or diabetic status represses CYP7A1 transcription and bile acid biosynthesis through SHP induction and FOXO1 inactivation, leading to impairment of the hepatic cholesterol/bile acid metabolisms.

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Section: Discussionmentioning

confidence: 99%

Insulin-dependent suppression of cholesterol 7α-hydroxlase is a possible link between glucose and cholesterol metabolisms

Park

Pak

2011

Exp Mol Med

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“…Increases of PAI-1 have been observed in cases of thrombosis and fibrosis, obesity, diabetes, and insulin resistance (Meigs et al, 2000;Ma et al, 2004). Increases in PAI-1 mRNA expression were reported in the atherosclerotic artery of type 2 diabetic patients (Pandolfi et al, 2001) and in VSMCs cultured under high glucose conditions (Suzuki et al, 2002) or angiotensin-II (Lee et al, 2010). However, the signaling pathway involved in high glucose-induced PAI-1 expression and proliferation of VSMCs is not clear even though MAPK or PKC activation is partially involved (Suzuki et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of NF-κB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells

Jeong

Park

et al. 2011

Exp Mol Med

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Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-κB (NF-κB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-κB activation. Also, we determined whether selective inhibition of NF-κB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-κB or expression of a recombinant adenovirus vector encoding an IκB-α mutant (Ad-IκBαM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-κB activation was determined by immunohistochemical staining, NF-κB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-κB activity. Treatment with inhibitors of NF-κB such as MG132, PDTC or expression of Ad-IκB-αM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-κB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression.

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“…Similarly, the ribosomal phosphoprotein P0 (Rplp0), the only outlier detected in the category of 60S ribosomal proteins, participates in protein complexes with other cytosolic proteins (Grap2 and cyclin D interacting protein) (99), and its free form has been implicated in other extra-ribosomal functions (100). Finally, PAI-1, the clearest example of an outlier changing in the same direction as its category, is a major mediator of the effect of AngII on VSMC (101). Together these results indicate that the outliers detected by the model correspond to proteins that are either incorrectly classified or play specific roles that are different from those of the other proteins in the category.…”

Section: Protein Outliers Maintain Their Noncoordinated Behavior Overmentioning

confidence: 77%

A Novel Systems-Biology Algorithm for the Analysis of Coordinated Protein Responses Using Quantitative Proteomics

Garcia-Marques

Trevisán-Herraz

Martı́nez-Martı́nez

et al. 2016

Molecular & Cellular Proteomics

109

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Orphan nuclear receptor small heterodimer partner inhibits angiotensin II-stimulated PAI-1 expression in vascular smooth muscle cells

Cited by 5 publications

References 37 publications

Insulin-dependent suppression of cholesterol 7α-hydroxlase is a possible link between glucose and cholesterol metabolisms

Insulin-dependent suppression of cholesterol 7α-hydroxlase is a possible link between glucose and cholesterol metabolisms

Inhibition of NF-κB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells

A Novel Systems-Biology Algorithm for the Analysis of Coordinated Protein Responses Using Quantitative Proteomics

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