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microRNA 146a is a critical regulator of inflammation that contributes to development of diabetic nephropathy (LB538)
Author(s) -
Bhatt Kirti
Publication year - 2014
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.28.1_supplement.lb538
Subject(s) - diabetic nephropathy , inflammation , diabetes mellitus , fibrosis , ctgf , microrna , medicine , kidney disease , endocrinology , streptozotocin , biology , immunology , gene , receptor , growth factor , biochemistry
microRNA 146a is a critical regulator of inflammation that contributes to development of diabetic nephropathy Kirti Bhatt, Linda Lanting, Ye Jia, Marpadga A Reddy, Mark Boldin, Rama Natarajan Departments of Diabetes and Molecular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010 Diabetic nephropathy (DN) is one of the leading causes of End Stage Renal Disease. Innate immunity and inflammation are known to play a role in the pathogenesis of diabetes and the associated complications. MicroRNAs have recently emerged as potent regulators of DN. However, the role of microRNAs in inflammation associated with the development of DN is not clearly understood. Here we examined the hypothesis that the anti‐inflammatory microRNA, miR‐146a may be dysregulated in DN and modulates disease progression. miR‐146a up regulation was consistently observed in the peritoneal macrophages as well as renal cortical tissues of diabetic mice. Importantly, key parameters of DN were significantly greater in diabetic miR‐146a deficient mice relative to wild type (WT). 16 weeks after induction of diabetes with streptozotocin, significant increase in proteinuria, macrophage infiltration, glomerular hypertrophy and fibrosis were observed in the miR‐146a null mice as compared to the WT group. Mechanistically, the expression of pro‐inflammatory (MCP‐1, TNF‐α) and pro‐fibrotic (TGF‐β, CTGF, Col1a2) genes was significantly elevated in the kidneys of diabetic miR‐146a null mice relative to WT. Furthermore, miR‐146a target genes Traf 6 and Irak 1 were up‐regulated in the renal cortical tissues of diabetic miR‐146a null mice as compared to the WT mice. Together, these results suggest that miR‐146a plays an anti‐inflammatory role in the kidney by negatively regulating inflammatory signaling and fibrosis to confer protection from the development of DN. They also suggest the novel involvement of inflammation and immune modulatory microRNA‐dependent mechanisms in DN.