Pioglitazone promotes preadipocyte proliferation by downregulating p16Ink4a
Pioglitazone promotes preadipocyte proliferation by downregulating p16Ink4a
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DOI：
10.1016/j.bbrc.2011.06.152
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发表时间：
2011-07-29
影响因子：
3.1
通讯作者：
Kohno, Masakazu
中科院分区：
文献类型：
--
作者：
Hasan, Arif U.;Ohmori, Koji;Kohno, Masakazu
吡格列酮是过氧化物酶体增殖物激活受体（PPAR）γ的一种合成配体，通过一种机制引起前脂肪细胞增殖，这种机制仍然是难以捉摸的。在这里，为了解决的机制，我们研究了PPAR γ和吡格列酮对细胞周期蛋白依赖性激酶抑制剂的动力学的影响，特别是与p16（Ink 4a）（p16）为中心，采用3 T3-L1前脂肪细胞。吡格列酮通过增加S和G（2）/M细胞周期进入促进前脂肪细胞增殖，同时伴有p16 mRNA表达降低。过氧化物酶体增殖物激活物受体γ过表达沿着荧光素酶报告基因检测证实，过氧化物酶体增殖物激活物受体γ对下调p16 mRNA转录至关重要，吡格列酮可增强该作用。因此，吡格列酮对前脂肪细胞增殖具有细胞周期依赖性促进作用，其机制包括通过PPAR γ下调p16。(C)2011 Elsevier Inc. All rights reserved.
Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR)gamma, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPAR gamma 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. PPAR gamma overexpression along with the luciferase reporter assay confirmed that PPAR gamma 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 PPAR gamma. (C) 2011 Elsevier Inc. All rights reserved.