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The prostaglandin F2alpha/calcineurin‐signaling pathway inhibits adipogenesis via the autocrine actions of an IL‐11/gp130/STAT1‐dependent signaling cascade
Author(s) -
Annamalai Damodaran,
Clipstone Neil A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1169.12
Subject(s) - adipogenesis , autocrine signalling , glycoprotein 130 , microbiology and biotechnology , calcineurin , signal transduction , adipocyte , paracrine signalling , stat1 , chemistry , transcription factor , biology , medicine , receptor , endocrinology , biochemistry , adipose tissue , transplantation , stat3 , mesenchymal stem cell , gene
Prostaglandin F2α (PGF2α) is a potent physiological inhibitor of adipocyte differentiation. In previous studies we have demonstrated that PGF2α inhibits adipogenesis via a signaling pathway that is dependent upon the activity of the calcium‐regulated protein phosphatase calcineurin. In the current study, we have extended these findings to further elucidate the mechanism by which the PGF2α/calcineurin‐pathway inhibits adipocyte differentiation. We now identify the IL‐11 cytokine, a member of the gp130 cytokine co‐receptor‐related family, as a downstream transcriptional target of this pathway in 3T3‐L1 preadipocytes. Using a combined shRNA and dominant‐negative mutant approach we provide evidence that IL‐11/gp130‐signaling is indeed required to mediate the inhibitory effects of PGF2α on adipogenesis. By taking advantage of a well‐characterized panel of chimeric gp130 mutant receptors, we demonstrate that gp130 signaling is sufficient to inhibit adipocyte differentiation and specifically requires the activation of the STAT1 transcription factor. Conversely, we find that depleting endogenous STAT1 levels rescues adipogenesis in the presence of both IL‐11 and PGF2α. Collectively, our findings support a model in which the PGF2α/calcineurin‐signaling pathway inhibits adipocyte differentiation via an autocrine IL‐11/gp130/STAT1‐dependent signaling cascade.