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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bouloumié, Anne Langin, Dominique Saulnier-blache, Jean Sébastien Rancoule, Chloé Bascands, Jean-loup Viguerie, Nathalie Viaud, Manon Gres, Sandra Valet, Philippe Decaunes, Pauline |
| Description | Author Affiliation: Rancoule C ( Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1048, Toulouse Cedex 4, France) |
| Abstract | 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 I, III, and IV collagens (COL), fibronectin (FN), TGFβ, CTGF and αSMA] 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 μM) and/or Ki16425 (10 μM) and/or the HIF-1α inhibitor YC-1 (100 μM). Treatment of db/db mice with Ki16425 reduced Col I 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 Col I and III, TGFβ and αSMA 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-1α. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 1 |
| Volume Number | 1841 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2014-01-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Adipose Tissue Metabolism Isoxazoles Toxicity Lysophospholipids Propionates Receptors, Lysophosphatidic Acid Antagonists & Inhibitors Actins Biosynthesis Pathology Animals Collagen Enzyme Activators Pharmacology Fibrosis Hypoxia-Inducible Factor 1, Alpha Subunit Indazoles Mice Mice, Obese Tissue Culture Techniques Transforming Growth Factor Beta Clinical Trial Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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