期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1841, 期 1, 页码 88-96出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2013.10.003
关键词
Lysophosphatidic acid; Adipose tissue; Fibrosis
资金
- University Paul Sabatier (Toulouse, France)
- INSERM
- Fondation pour la Recherche Medicale [DRM20101220459]
- Region Midi Pyrenees
- Commission of the European Communities (Project ADAPT) [HEALTH-F2-2008-2011 00]
Lysophosphatidic acid (LPA) is a pro-fibrotic mediator acting via specific receptors (LPARs) and is synthesized by autotaxin, that increases with obesity. We tested whether LPA could play a role in adipose tissue (AT)-fibrosis associated with obesity. Fibrosis [type 1, III, and IV collagens (COL), fibronectin (FN), TGF beta, CTGF and alpha SMA] and inflammation (MCP1 and F4/80) markers were quantified: (i) in vivo in inguinal (IAT) and perigonadic (PGAT) AT from obese-diabetic db/db mice treated with the LPAR antagonist Ki16425 (5 mg/kg/day ip for 7 weeks); and (ii) in vitro in human AT explants in primary culture for 72 h in the presence of oleoyl-LPA (10 mu M) and/or Ki16425 (10 mu M) and/or the HIF-1 alpha inhibitor YC-1 (100 mu M). Treatment of db/db mice with Ki16425 reduced Coil and IV mRNAs in IAT and PGAT while Col III mRNAs were only reduced in IAT. This was associated with reduction of COL protein staining in both IAT and PGAT. AT explants showed a spontaneous and time-dependent increase in ATX expression and production of LPA in the culture medium, along with increased levels of Coil and III, TGF beta and aSMA mRNAs and of COL protein staining. In vitro fibrosis was blocked by Ki16425 and was further amplified by oleoyl-LPA. LPA-dependent in vitro fibrosis was blocked by co-treatment with YC1. Our results show that endogenous and exogenous LPA exert a pro-fibrotic activity in AT in vivo and in vitro. This activity could be mediated by an LPA1R-dependent pathway and could involve HIF-1 alpha. (C) 2013 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据