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Mol Endocrinol. 2009 Nov;23(11):1876-84. doi: 10.1210/me.2009-0117. Epub 2009 Oct 9.

MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1.

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1
Department of Metabolic Discovery Technology Group, GlaxoSmithKline, Inc., Research Triangle Park, North Carolina 27709, USA. jaystrum@msn.com

Abstract

Human adipose tissue secretes a number of proinflammatory mediators that may contribute to the pathophysiology of obesity-related disorders. Understanding the regulatory pathways that control their production is paramount to developing effective therapeutics to treat these diseases. Using primary human adipose-derived stem cells as a source of preadipocytes and in vitro differentiated adipocytes, we found IL-8 and monocyte chemoattractant protein-1 (MCP-1) are constitutively secreted by both cell types and induced in response to serum deprivation. MicroRNA profiling revealed the rapid induction of microRNA 132 (miR-132) in these cells when switched to serum-free medium. Furthermore, miR-132 overexpression was sufficient to induce nuclear factor-kappaB translocation, acetylation of p65, and production of IL-8 and MCP-1. Inhibitors of miR-132 decreased acetylated p65 and partially inhibited the production of IL-8 and MCP-1 induced by serum deprivation. MiR-132 was shown to inhibit silent information regulator 1 (SirT1) expression through a miR-132 binding site in the 3'-untranslated region of SirT1. Thus, in response to nutritional availability, induction of miR-132 decreases SirT1-mediated deacetylation of p65 leading to activation of nuclear factor-kappaB and transcription of IL-8 and MCP-1 in primary human preadipocytes and in vitro differentiated adipocytes.

PMID:
19819989
DOI:
10.1210/me.2009-0117
[Indexed for MEDLINE]
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