Abstract P137: Mir-122 is Associated With Stress-response Protein, Hemeoxygenase-1, for Regulation of Extracellular Matrix Remodeling in Renal Hypertension

Abstract

Oxidative stress is a major contributing factor in hypertension-induced kidney injury. Hemeoxygenase-1 (Ho-1) is stress response protein constitutively expressed by the proximal tubular epithelial cells in response to oxidative stress. MicroRNAs are single stranded RNA involved in the regulation of gene expression. MicroRNA-122 has been shown to regulate Ho-1 expression in hepatitis; however whether miR-122 regulates Ho-1 in hypertensive kidney is not known. The purpose of the study was to investigate the miRNA-122 Ho-1 regulation and determine its role in extracellular matrix remodeling in renal hypertension. In vitro experiments were done using mesangial cells, treated with/without 200 μM of Angiotensin-II (Ang-II). Ho-1 was induced by ~3.5 folds with Ang-II treatment. miR-122, Ho-1 regulator, was downregulated by >15 times in Ang-II treated cells. In vivo experiments were performed on WT (C57BL6/J) mice aged 12-14 wk and 75-78 wk. The animals were treated with Ang-II (1000ng/kg/min) for 4 weeks. Ho-1 is ~6 folds less in kidney of aged mice as compared to that in the young mice. Hypertension increases miR-122 expression to a greater extent (~5 folds) in aged animals. In Ho-1 knocked down mesangial cells, the extracellular matrix component, Collagen 1A1 (Col1a1), was increased by ~2 folds. In contrast, vascular endothelial growth factor ( Vegf ) and hypoxia-inducible factor ( Hif1 α ) were downregulated in Ho-1 depleted cells. In conclusion, micro RNA, miR-122, transcriptionally regulates Ho-1 as a repressor in kidney and thus affects Ho-1 mediated regulation of the extracellular remodeling in hypertension-induced renal damage.