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Resistin derived from diabetic perivascular adipose tissue up‐regulates vascular expression of osteopontin via the AP ‐1 signalling pathway
Author(s) -
Park So Youn,
Kim Kyu Hee,
Seo Kyo Won,
Bae Jin Ung,
Kim Yun Hak,
Lee Seung Jin,
Lee Won Suk,
Kim Chi Dae
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4286
Subject(s) - resistin , adipokine , medicine , osteopontin , endocrinology , adipose tissue , adipocyte , chemistry , biology , microbiology and biotechnology , diabetes mellitus , insulin resistance
Perivascular adipose tissue ( PVAT ) is implicated in the development of vascular diseases; however, the roles of PVAT on OPN expression in diabetic vasculature remain to be determined. This study investigated the role of adipokines derived from diabetic PVAT in regulating the vascular expression of OPN and explored the mechanisms involved. Aortic sections of ob/ob and high‐fat diet ( HFD )‐induced obese ( DIO ) mice showed an increased expression of OPN , which was paralleled by increased amounts of PVAT characterized by enlargement of adipocytes. In the earlier phase of HFD feeding, macrophage infiltration was mainly localized to the area of PVAT at which adipocytes were enlarged, suggesting a potential link of activated adipocytes to macrophage infiltration. PVAT sections of ob/ob and DIO mice revealed a significantly greater number of macrophages with increased expression of adipokines, including resistin and visfatin. The distribution of resistin in PVAT mostly co‐localized with macrophages, while visfatin was expressed in macrophages and other cells. In in vitro studies, OPN expression in vascular smooth muscle cells ( VSMCs ) co‐cultured with PVAT of DIO mice was significantly increased, which was attenuated by a resistin‐neutralizing antibody. Likewise, resistin up‐regulated expression of OPN mRNA and protein in cultured VSMCs and the pivotal role of AP ‐1 in resistin‐induced OPN transcription was demonstrated. Resistin produced by PVAT plays a pivotal role in the up‐regulated expression of OPN in the diabetic vasculature via a signalling pathway that involves activation of AP ‐1. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britainand Ireland.