A1046 MicroRNA-29b Ameliorates Hypertensive Renal Dysfunction via Suppression of the TGF-β-induced epithelial-mesenchymal transition and extracellular matrix synthesis

Abstract

Objectives: MicroRNA-29b (miR-29b) has been recently reported to regulate fibrosis in renal diseases. However, very little is known about its functional role in hypertensive nephropathy. Here we studied whether alterations in miR-29b expression contribute to hypertension-induced renal dysfunction and renal fibrosis. Methods: Renal function was monitored by measuring the contents of serum creatinine (SCr), blood urea nitrogen (BUN) and urinary protein (UP) after treatment with a high efficient lentivector encoding miR-29b mimics or inhibitor. Collagen I, α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) were evaluated at gene expression and protein levels by PCR and Western blot analysis, respectively. The degree of renal fibrosis was determined using Sirius red staining. Meanwhile, immunohistostaining was performed to identify the distribution of collagen I, α-SMA and TGF- β as well. Results: MiR-29b overexpression and knockdown significantly inhibited and increased serum creatinine (P < 0.05), urea nitrogen (P < 0.05) and urinary protein levels (P < 0.05) in SHRs. Importantly, miR-29b overexpression in SHRs lowed the urinary protein content by 6.75% compared with the normotensive controls. The interstitial deposition of collagen I, α-SMA and TGF-β expression were dramatically decreased when miR-29b level was augmented. In contrast, knockdown of miR-29b promoted TGF-β induced expression of collagen I and α-SMA both on a gene and on a protein level. Moreover, a negative regulatory role of miR-29b on the expression of TGF-β was clarified during the process of hypertensive nephropathy. Conclusion: MiR-29b may serve as an anti-fibrotic target by down-regulation of TGF-β in the pathophysiology of hypertension related renal fibrosis. Administration of an agent that increases miR-29b function prevents re