TY - JOUR
T1 - Reduction of PP2A Cα stimulates adipogenesis by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression
AU - Okamura, Hirohiko
AU - Yang, Di
AU - Yoshida, Kaya
AU - Teramachi, Jumpei
AU - Haneji, Tatsuji
N1 - Funding Information:
We would like to thank Ms. E. Sasaki for her skillful technical assistance. We also thank the Support Center for Advanced Medical Sciences, Institute of Health Biosciences, the University of Tokushima Graduate School, for technical support. This study was supported by grants from the Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan ( 23592703 , HO), the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, and Takeda Science Foundation.
PY - 2014/11
Y1 - 2014/11
N2 - 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 Cα in adipocyte differentiation. PP2A Cα expression and PP2A activity decreased during adipocyte differentiation in C3H10T1/2 and 3T3-L1 cells and the expression of adipocyte marker genes such as PPARγ and adiponectin increased. To further clarify the role of PP2A Cα in adipocyte differentiation, we constructed PP2A knockdown cells by infecting C3H10T1/2 cells with a lentivirus expressing a shRNA specific for the PP2A Cα (shPP2A cells). Silencing of PP2A Cα in C3H10T1/2 cells dramatically stimulated adipocyte differentiation and lipid accumulation, which were accompanied by expression of adipocyte marker genes. Silencing of PP2A Cα suppressed Wnt10b expression and reduced the levels of the inactivated form of GSK-3β (phospho-GSK-3β), leading to the reduction of β-catenin levels in the nucleus and its transcriptional activity. Treatment with LiCl, a GSK-3β inhibitor, and inhibition of PPARγ expression suppressed the accelerated adipogenesis of shPP2A cells. Our data indicate that PP2A Cα plays an important role in the regulation of adipocyte differentiation by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression.
AB - 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 Cα in adipocyte differentiation. PP2A Cα expression and PP2A activity decreased during adipocyte differentiation in C3H10T1/2 and 3T3-L1 cells and the expression of adipocyte marker genes such as PPARγ and adiponectin increased. To further clarify the role of PP2A Cα in adipocyte differentiation, we constructed PP2A knockdown cells by infecting C3H10T1/2 cells with a lentivirus expressing a shRNA specific for the PP2A Cα (shPP2A cells). Silencing of PP2A Cα in C3H10T1/2 cells dramatically stimulated adipocyte differentiation and lipid accumulation, which were accompanied by expression of adipocyte marker genes. Silencing of PP2A Cα suppressed Wnt10b expression and reduced the levels of the inactivated form of GSK-3β (phospho-GSK-3β), leading to the reduction of β-catenin levels in the nucleus and its transcriptional activity. Treatment with LiCl, a GSK-3β inhibitor, and inhibition of PPARγ expression suppressed the accelerated adipogenesis of shPP2A cells. Our data indicate that PP2A Cα plays an important role in the regulation of adipocyte differentiation by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression.
KW - Adipogenesis
KW - PPARγ
KW - Protein phosphatase 2A
KW - Wnt/GSK-3β/β-catenin
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U2 - 10.1016/j.bbamcr.2014.06.008
DO - 10.1016/j.bbamcr.2014.06.008
M3 - Article
AN - SCOPUS:84905178655
SN - 0167-4889
VL - 1843
SP - 2376
EP - 2384
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 11
ER -