Caveolin-1 and Integrin β1 Regulate Embryonic Stem Cell Proliferation via p38 MAPK and FAK in High Glucose

The involvement of caveolin-1 (Cav-1) and integrin beta 1 (IN beta 1) in regulation of embryonic stem (ES) cell growth by high glucose is by no means clear cut. Therefore, the aim of this study was to examine the influence of high glucose on Cav-1 and IN beta 1 expression in mouse ES cells and their signaling pathways to modulate proliferation. High glucose significantly increased Cav-1 and IN beta 1 expression. In addition, increased IN beta 1 expression was inhibited by Cav-1 small interfering RNA (siRNA). High glucose caused reactive oxygen species generation and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Inhibition of p38 MAPK blocked high glucose-induced Cav-1 and fibronectin (FN) expression. Moreover, phosphorylation of both Src and focal adhesion kinase (FAK) were increased by high glucose, which were inhibited by IN beta 1 antibody. In addition, high glucose increased the expression levels of PINCH 1/2, integrin-linked kinase (ILK), and a-parvin [PIP] complex proteins, which were all inhibited by the FAK siRNA and Src specific inhibitor (PP2, 10(-7) M). High glucose also increased F-actin expression, which was inhibited by ILK, PINCH 1/2, and alpha-parvin siRNAs. Finally, high glucose-induced increase of ES cell proliferation was inhibited by TRIO and F-actin binding protein (TRIOBP) siRNA. The results demonstrate that high glucose-induced Cav-1 and IN beta 1 activation can stimulate ES cell proliferation through the modification of focal adhesion signaling pathways. J. Cell. Physiol. 226: 1850-1859, 2011. (C) 2010 Wiley-Liss, Inc.