title: Reduction of PP2A Cα stimulates adipogenesis by regulating the Wnt/GSK-3β/β-catenin pathway and PPARγ expression.
abstract: 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.
authors.affiliation: Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto, Tokushima 770-8504, Japan. Electronic address: okamura@tokushima-u.ac.jp.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Di
authors.initials: D
authors.lastname: Yang
authors.affiliation: Oral Health Care Education, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Kaya
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Teramachi
authors.affiliation: Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Haneji
keywords: Adipogenesis; PPARγ; Protein phosphatase 2A; Wnt/GSK-3β/β-catenin