Biochemical and histological impact of direct renin inhibition by aliskiren on myofibroblasts activation and differentiation in bleomycin induced pulmonary fibrosis in adult mice

摘要

Aliskiren is a drug classified as a direct renin inhibitor. The renin-angiotensin system plays an important role in pulmonary fibrogeneses. This study aimed to investigate the impact of aliskiren on pulmonary fibrosis induced by bleomycin. Forty adult mice were divided into group I (control), group II (aliskiren 25 mg/kg/day IP), group III (bleomycin 0.035 U/g intraperitoneally twice weekly for 4 weeks) and group IV (aliskiren + bleomycin). Plasma renin activity (PRA), lung content of hydroxyproline and transforming growth factor-beta 1 (TGF-beta 1) were assayed. Lung paraffin sections were prepared for histological study and immunohistochemical detection of alpha smooth muscle actin (alpha SMA) as a marker for myofibroblasts activation and differentiation. Bleomycin induced a significant elevation of PRA with a significant increase in hydroxyproline and TGF-beta 1 in group III. Microscopically, pulmonary fibrosis was evident in the form of areas of collapsed alveoli, intense inflammatory cells infiltrations, excess accumulation of collagen, and excessively encountered alpha SMA positively immune-stained myofibroblasts, compared to a negative immune-reaction in groups I and II. In group IV, aliskiren resulted in a significant decrease in PRA, TGF-beta 1 and hydroxyproline, with an attenuation of pulmonary fibrosis and a decrease in alpha SMA positively immune-stained myofibroblasts. In conclusion, renin inhibition by aliskiren attenuated pulmonary fibrosis through decreasing TGF-beta 1 and myofibroblasts activation and differentiation. (C) 2015 Elsevier Ltd. All rights reserved.