title: Identification of a microRNA signature in renal fibrosis: role of miR-21.
abstract: Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Zarjou
authors.forename: Shanzhong
authors.initials: S
authors.lastname: Yang
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Anupam
authors.initials: A
authors.lastname: Agarwal
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: C524940:MIRN21 microRNA, human; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha