Reduction of PP2A Cα stimulates adipogenesis by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression
Reduction of PP2A Cα stimulates adipogenesis by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression
复制标题
DOI：
10.1016/j.bbamcr.2014.06.008
复制
发表时间：
2014-11-01
影响因子：
5.1
通讯作者：
Haneji, Tatsuji
中科院分区：
文献类型：
--
作者：
Okamura, Hirohiko;Yang, Di;Haneji, Tatsuji
丝氨酸/苏氨酸蛋白磷酸酶2A（PP 2A）调节多种生理过程，如细胞周期、细胞生长、凋亡和信号转导。在这项研究中，我们研究了PP 2A C α在脂肪细胞分化中的表达和作用。在C3 H10 T1/2和3 T3-L1细胞中，在脂肪细胞分化过程中，PP 2A C α表达和PP 2A活性降低，而脂肪细胞标记基因如PPAR γ和脂联素的表达增加。为了进一步阐明PP 2A C α在脂肪细胞分化中的作用，我们通过用表达PP 2A C α特异性shRNA的慢病毒感染C3 H10 T1/2细胞（shPP 2A细胞）来构建PP 2A敲除细胞。在C3 H10 T1/2细胞中，PP 2A C α的沉默显著刺激脂肪细胞分化和脂质积累，这伴随着脂肪细胞标记基因的表达。PP 2A C α的沉默抑制了Wnt 10 b的表达，并降低了GSK-3 β（磷酸化GSK-3 β）的失活形式的水平，导致细胞核中β-连环蛋白水平及其转录活性的降低。用GSK-3 β抑制剂LiCl处理和抑制PPAR γ表达抑制了shPP 2A细胞的加速脂肪形成。我们的数据表明，PP 2A C α通过调节Wnt/GSK-3 β/β-连环蛋白通路和PPAR γ表达在脂肪细胞分化的调节中起重要作用。(C)2014由Elsevier B. V.出版
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 C alpha in adipocyte differentiation. PP2A C alpha expression and PP2A activity decreased during adipocyte differentiation in C3H10T1/2 and 3T3-L1 cells and the expression of adipocyte marker genes such as PPAR gamma and adiponectin increased. To further clarify the role of PP2A C alpha in adipocyte differentiation, we constructed PP2A knockdown cells by infecting C3H10T1/2 cells with a lentivirus expressing a shRNA specific for the PP2A C alpha (shPP2A cells). Silencing of PP2A C alpha in C3H10T1/2 cells dramatically stimulated adipocyte differentiation and lipid accumulation, which were accompanied by expression of adipocyte marker genes. Silencing of PP2A C alpha suppressed Wnt10b expression and reduced the levels of the inactivated form of GSK-3 beta (phospho-GSK-3 beta), leading to the reduction of beta-catenin levels in the nucleus and its transcriptional activity. Treatment with LiCl, a GSK-3 beta inhibitor, and inhibition of PPAR gamma expression suppressed the accelerated adipogenesis of shPP2A cells. Our data indicate that PP2A C alpha plays an important role in the regulation of adipocyte differentiation by regulating the Wnt/GSK-3 beta/beta-catenin pathway and PPAR gamma expression. (C) 2014 Published by Elsevier B.V.