Publications [#86228] of Anna Mae Diehl

Papers Published

1. C Zhao, W Chen, L Yang, L Chen, SA Stimpson, AM Diehl, PPARgamma agonists prevent TGFbeta1/Smad3-signaling in human hepatic stellate cells., Biochemical and biophysical research communications, vol. 350 no. 2 (November, 2006), pp. 385-91, ISSN 0006-291X [doi]
   (last updated on 2013/05/16)

   Abstract:
   PPARgamma agonists inhibit liver fibrosis, but the mechanisms involved are uncertain. We hypothesized that PPARgamma agonists inhibit transforming growth factor (TGF)beta1-activation of TGFbeta receptor (TGFbetaR)-1 signaling in quiescent stellate cells, thereby abrogating Smad3-dependent induction of extracellular matrix (ECM) genes, such as PAI-1 and collagen-1alphaI. To test this, human HSC were cultured to induce a quiescent phenotype, characterized by lipid accumulation and PPARgamma expression and transcriptional activity. These adipocytic HSC were then treated with TGFbeta1+/-a TGFbetaR-1 kinase inhibitor (SB431542) or a PPARgamma agonist (GW7845). TGFbeta1 caused dose- and time-dependent increases in Smad3 phosphorylation, followed by induction of collagen and PAI-1 expression. Like the TGFbetaR-1 kinase inhibitor, the PPARgamma agonist caused dose-dependent inhibition of all of these responses without effecting HSC proliferation or viability. Thus, the anti-fibrotic actions of PPARgamma agonists reflect their ability to inhibit TGFbeta1-TGFbetaR1 signaling that initiates ECM gene expression in quiescent HSC.

   Keywords:
   Activin Receptors, Type I • Adipocytes • Benzamides • Cell Line • Culture Media • Dioxoles • Extracellular Matrix Proteins • Gene Expression • Humans • Liver • Oxazoles • PPAR gamma • Phosphorylation • Protein Kinase Inhibitors • Protein-Serine-Threonine Kinases • Receptors, Transforming Growth Factor beta • Signal Transduction • Smad3 Protein • Transforming Growth Factor beta1 • Tyrosine • agonists* • analogs & derivatives • antagonists & inhibitors • antagonists & inhibitors* • biosynthesis • cytology • cytology* • drug effects • genetics • metabolism • pharmacology