title: Caveolin-1 and integrin β1 regulate embryonic stem cell proliferation via p38 MAPK and FAK in high glucose.
abstract: The involvement of caveolin-1 (Cav-1) and integrin β1 (IN β1) 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 β1 expression in mouse ES cells and their signaling pathways to modulate proliferation. High glucose significantly increased Cav-1 and IN β1 expression. In addition, increased IN β1 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 β1 antibody. In addition, high glucose increased the expression levels of PINCH1/2, integrin-linked kinase (ILK), and α-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, PINCH1/2, and α-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 β1 activation can stimulate ES cell proliferation through the modification of focal adhesion signaling pathways.
authors.affiliation: Department of Veterinary Physiology, Biotherapy Human Resources Center (BK 21), College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Park
authors.forename: Hyoung Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D000185:Actinin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000201:enzymology*; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D000185:Actinin; D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D051242:Caveolin 1; D004268:DNA-Binding Proteins; D005353:Fibronectins; D051417:Focal Adhesion Kinase 1; D005947:Glucose; D019012:Integrin beta1; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases; D000099200:Scaffold Protein ILK; C495541:Cav1 protein, mouse; C490232:Lims1 protein, mouse; C490234:Lims2 protein, mouse; C519774:Parva protein, mouse; C500559:Parvb protein, mouse; C550098:TRIOBP protein, mouse; C496051:Ptk2 protein, mouse