Objectives Primary study have demonstrated that the Angiotensin II (Ang II) contents and the its receptor density in the kidney of young spontaneously hypertensive rats (SHR) were significantly higher than age-matched Wistar-Kyoto rats (WKY). Ang II has been shown to induce renal fibrosis, including Epithelial-Mesenchymal Transition (EMT) and tubulointerstitial fibrosis. This study investigated the role of microRNAs (miRNAs) in renal fibrosis induced by Ang II.
Methods Differential expression of miRNAs in renal cortex between young SHR and age-matched WKY was demonstrated by miRNA microarray, and confirmed by real-time PCR.
Results The miR-29b was down-regulated by 48% in SHR. In NRK-52E renal tubular epithelial cells and NRK-49F renal interstitial fibroblasts, treatment withAng II reduced the expression of miR-29b. Down-regulation of miR-29b by transfection of miR-29b inhibitor significantly increased the expression of transforming growth factor (TGF-β), α-smooth muscle actin (α-SMA), Collagen (Col ) of NRK-52E cells and the expression of TGF-β, Col and matrix metalloproteinase-2 (MMP-2) of NRK-49F cells. Treatment of 10-7M Ang II caused similar result, while up-regulation of miR-29b by transfection of miR-29b mimics 24 hrs before Treatment of Ang II resulted in obvious down-regulation of these genes.
Conclusions We conclude that miR-29b is down-regulated in renal cortex of young SHR and may participate in renal fibrosis induced by Ang II.