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Loss of microRNA-192 promotes fibrogenesis in diabetic nephropathy

Krupa, Aleksandra, Jenkins, Robert Hywel, Luo, Dong Dong, Lewis, Aled G., Phillips, Aled Owain and Fraser, Donald James 2010. Loss of microRNA-192 promotes fibrogenesis in diabetic nephropathy. Journal of the American Society of Nephrology 21 (3) , pp. 438-447. 10.1681/ASN.2009050530

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Abstract

The role of microRNAs (miRs), which are endogenous RNA oligonucleotides that regulate gene expression, in diabetic nephropathy is unknown. Here, we performed expression profiling of cultured proximal tubular cells (PTCs) under high-glucose and control conditions. We identified expression of 103 of 328 microRNAs but did not observe glucose-induced changes in expression. Next, we performed miR expression profiling in pooled RNA from formalin-fixed, paraffin-embedded tissue from renal biopsies. We studied three groups of patients with established diabetic nephropathy and detected 103 of 365 miRs. Two miRs differed by more than two-fold between progressors and nonprogressors, and 12 miRs differed between late presenters and other biopsies. We noted the greatest change in miR-192 expression, which was significantly lower in late presenters. Furthermore, in individual biopsies, low expression of miR-192 correlated with tubulointerstitial fibrosis and low estimated GFR. In vitro, treatment of PTCs with TGF-β1 decreased miR-192 expression. Overexpression of miR-192 suppressed expression of the E-Box repressors ZEB1 and ZEB2, thereby opposing TGF-β–mediated downregulation of E-cadherin. In summary, loss of miR-192 expression associates with increased fibrosis and decreased estimated GFR in diabetic nephropathy in vivo, perhaps by enhancing TGF-β–mediated downregulation of E-cadherin in PTCs.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: Lippincott, Williams & Wilkins
ISSN: 1046-6673
Last Modified: 09 Nov 2017 21:49
URI: http://orca-mwe.cf.ac.uk/id/eprint/30081

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