title: Pioglitazone promotes preadipocyte proliferation by downregulating p16(Ink4a).
abstract: Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR)γ, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPARγ and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16(Ink4a) (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G(2)/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPARγ overexpression along with the luciferase reporter assay confirmed that PPARγ was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPARγ.
authors: Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors: Arif U
authors: AU
authors: Hasan
authors: Koji
authors: K
authors: Ohmori
authors: Takeshi
authors: T
authors: Hashimoto
authors: Kazuyo
authors: K
authors: Kamitori
authors: Yuko
authors: Y
authors: Hirata
authors: Yasuhiro
authors: Y
authors: Ishihara
authors: Naoko
authors: N
authors: Okamoto
authors: Takahisa
authors: T
authors: Noma
authors: Hiroaki
authors: H
authors: Kosaka
authors: Masaaki
authors: M
authors: Tokuda
authors: Masakazu
authors: M
authors: Kohno
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000037:antagonists & inhibitors* / Q000235:genetics; D015536:Down-Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077205:Pioglitazone