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• W2067385280 endingPage "29794" @default.
• W2067385280 startingPage "29784" @default.
• W2067385280 abstract "Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) down-regulates the expression of follistatin mRNA in intestinal epithelial cells in vivo. The mechanism of PPARgamma-mediated down-regulation of follistatin was investigated using non-transformed, rat intestinal epithelial cells (RIE-1). RIE cells expressed activin A, the activin receptors ActRI and ActRII, and the follistatin-315 mRNA. RIE-1 cells responded to endogenous activin A, and this response was antagonized by follistatin, as evidenced by changes in cell growth and regulation of an activin-responsive reporter. Using RIE-1 cells, we show that activation of PPARgamma by rosiglitazone reduced follistatin mRNA levels in a dose- and concentration-dependent manner. Down-regulation of follistatin by rosiglitazone required the DNA binding domain of PPARgamma and was dependent upon dimerization with the retinoid X receptor. Inhibition of follistatin expression by rosiglitazone was not associated with decreased follistatin mRNA stability, suggesting that regulation may be at the promoter level. Analysis of the follistatin promoter revealed consensus binding sites for AP-1, AP-2, and Sp1. Targeting the AP-1 pathway with SP600125, an inhibitor of JNK, and TAM67, a dominant negative c-Jun, had no effect on PPARgamma-mediated down-regulation of follistatin. However, the follistatin promoter was dramatically regulated by Sp1, and this regulation was inhibited by PPARgamma expression. Knockdown of Sp1 expression relieved repression of follistatin levels by rosiglitazone. Moreover, PPARgamma was found to interact with Sp1 and repress its transcriptional activation function. Collectively, our data indicate that repression of Sp1 transcriptional activity by PPARgamma is the underlying mechanism responsible for PPARgamma-mediated regulation of follistatin expression." @default.
• W2067385280 created "2016-06-24" @default.
• W2067385280 creator A5026692399 @default.
• W2067385280 creator A5038191637 @default.
• W2067385280 creator A5054696391 @default.
• W2067385280 date "2008-10-01" @default.
• W2067385280 modified "2023-09-27" @default.
• W2067385280 title "Peroxisome Proliferator-activated Receptor γ Down-regulates Follistatin in Intestinal Epithelial Cells through SP1" @default.
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• W2067385280 doi "https://doi.org/10.1074/jbc.m804481200" @default.
• W2067385280 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2662057" @default.
• W2067385280 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18768463" @default.
• W2067385280 hasPublicationYear "2008" @default.
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