PMID- 19819989 OWN - NLM STAT- MEDLINE DCOM- 20100217 LR - 20240109 IS - 1944-9917 (Electronic) IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 23 IP - 11 DP - 2009 Nov TI - MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1. PG - 1876-84 LID - 10.1210/me.2009-0117 [doi] AB - 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. FAU - Strum, Jay C AU - Strum JC AD - Department of Metabolic Discovery Technology Group, GlaxoSmithKline, Inc., Research Triangle Park, North Carolina 27709, USA. jaystrum@msn.com FAU - Johnson, Jennifer H AU - Johnson JH FAU - Ward, James AU - Ward J FAU - Xie, Hongbo AU - Xie H FAU - Feild, John AU - Feild J FAU - Hester, Austin AU - Hester A FAU - Alford, Alexander AU - Alford A FAU - Waters, K Michelle AU - Waters KM LA - eng PT - Journal Article DEP - 20091009 PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (3' Untranslated Regions) RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Interleukin-8) RN - 0 (MIRN132 microRNA, human) RN - 0 (MicroRNAs) RN - EC 3.5.1.- (SIRT1 protein, human) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - 3' Untranslated Regions MH - Adipocytes/metabolism MH - Adipose Tissue/cytology MH - Adult MH - Binding Sites MH - Chemokine CCL2/metabolism MH - Chemokines/*metabolism MH - Female MH - *Gene Expression Regulation MH - Humans MH - Interleukin-8/metabolism MH - MicroRNAs/genetics/*metabolism MH - *Nutritional Sciences MH - Sirtuin 1/metabolism/*physiology MH - Stem Cells/cytology PMC - PMC5419165 EDAT- 2009/10/13 06:00 MHDA- 2010/02/18 06:00 PMCR- 2010/11/01 CRDT- 2009/10/13 06:00 PHST- 2009/10/13 06:00 [entrez] PHST- 2009/10/13 06:00 [pubmed] PHST- 2010/02/18 06:00 [medline] PHST- 2010/11/01 00:00 [pmc-release] AID - me.2009-0117 [pii] AID - 10.1210/me.2009-0117 [doi] PST - ppublish SO - Mol Endocrinol. 2009 Nov;23(11):1876-84. doi: 10.1210/me.2009-0117. Epub 2009 Oct 9.