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dc.contributor.authorGe, Jianfeng
dc.contributor.authorBurnier, Laurent
dc.contributor.authorAdamopoulou, Maria
dc.contributor.authorKwa, Mei Qi
dc.contributor.authorSchaks, Matthias
dc.contributor.authorRottner, Klemens
dc.contributor.authorBrakebusch, Cord
dc.date.accessioned2018-11-20T11:34:14Z
dc.date.available2018-11-20T11:34:14Z
dc.date.issued2018-06-15
dc.identifier.issn1083-351X
dc.identifier.pmid29700112
dc.identifier.doi10.1074/jbc.RA117.001113
dc.identifier.urihttp://hdl.handle.net/10033/621574
dc.description.abstractMesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGF -induced myofibroblast differentiation of MSC, we generated a novel MSC line and its descendants lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGF -induced expression of -smooth muscle actin (SMA) but not of collagen I 1 (col1a1). Whereas loss of RhoA and Cdc42 reduced SMA expression, ablation of the Rac1 gene had the opposite effect. Although actin polymerization and MRTFa were crucial for TGF -induced SMA expression, neither Arp2/3-dependent actinpolymerizationnorcofilin-dependent severinganddepolymerization of F-actin were required. Instead, F-actin levels were dependent on cell contraction, and TGF -induced actin polymerization correlated with increased cell contraction mediated by RhoA and Cdc42. Finally, we observed impaired collagen I secretion in MSC lacking RhoA or Cdc42. These data give novel molecular insights into the role of Rho GTPases in TGF signaling and have implications for our understanding of MSC function in fibrosis.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectArp2/3 complexen_US
dc.subjectGTPaseen_US
dc.subjectMRTFaen_US
dc.subjectRac (Rac GTPase)en_US
dc.subjectRho GTPaseen_US
dc.subjectSMAD transcription factoren_US
dc.subjectTGFβen_US
dc.subjectcell differentiationen_US
dc.subjectcell signalingen_US
dc.subjectcytoskeletonen_US
dc.subjectmesenchymal stem cellen_US
dc.subjectmolecular cell biologyen_US
dc.subjectmyofibroblasten_US
dc.subjectp38en_US
dc.subjectstem cellsen_US
dc.subjectαSMAen_US
dc.titleRhoA, Rac1, and Cdc42 differentially regulate αSMA and collagen I expression in mesenchymal stem cells.en_US
dc.typeArticleen_US
dc.source.journaltitleThe Journal of biological chemistry


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