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Publication : Reduction of PP2A Cα stimulates adipogenesis by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression.

First Author  Okamura H Year  2014
Journal  Biochim Biophys Acta Volume  1843
Issue  11 Pages  2376-84
PubMed ID  24949891 Mgi Jnum  J:217948
Mgi Id  MGI:5616271 Doi  10.1016/j.bbamcr.2014.06.008
Citation  Okamura H, et al. (2014) Reduction of PP2A Calpha stimulates adipogenesis by regulating the Wnt/GSK-3beta/beta-catenin pathway and PPARgamma expression. Biochim Biophys Acta 1843(11):2376-84
abstractText  Serine/threonine protein phosphatase 2A (PP2A) regulates several physiological processes such as the cell cycle, cell growth, apoptosis, and signal transduction. In this study, we examined the expression and role of PP2A Calpha in adipocyte differentiation. PP2A Calpha expression and PP2A activity decreased during adipocyte differentiation in C3H10T1/2 and 3T3-L1 cells and the expression of adipocyte marker genes such as PPARgamma and adiponectin increased. To further clarify the role of PP2A Calpha in adipocyte differentiation, we constructed PP2A knockdown cells by infecting C3H10T1/2 cells with a lentivirus expressing a shRNA specific for the PP2A Calpha (shPP2A cells). Silencing of PP2A Calpha in C3H10T1/2 cells dramatically stimulated adipocyte differentiation and lipid accumulation, which were accompanied by expression of adipocyte marker genes. Silencing of PP2A Calpha suppressed Wnt10b expression and reduced the levels of the inactivated form of GSK-3beta (phospho-GSK-3beta), leading to the reduction of beta-catenin levels in the nucleus and its transcriptional activity. Treatment with LiCl, a GSK-3beta inhibitor, and inhibition of PPARgamma expression suppressed the accelerated adipogenesis of shPP2A cells. Our data indicate that PP2A Calpha plays an important role in the regulation of adipocyte differentiation by regulating the Wnt/GSK-3beta/beta-catenin pathway and PPARgamma expression.
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