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Eur Respir J. 2012 Jan;39(1):141-8. doi: 10.1183/09031936.00130310. Epub 2011 Jun 9.

Renin is an angiotensin-independent profibrotic mediator: role in pulmonary fibrosis.

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1
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.

Abstract

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is probably the result of interplay between cytokines/chemokines and growth factors. The renin-angiotensin (Ang) system is involved, although its profibrotic effect is attributed to Ang II. However, recent studies suggest that renin, through a specific receptor, is implicated in fibrogenesis. In this study, the expression of renin and renin receptor was examined in normal and IPF lungs and fibroblasts. Normal human lung fibroblasts were stimulated with renin or transfected with renin small interfering RNA (siRNA), and the expression of transforming growth factor (TGF)-β1 and α-1-type I collagen was analysed. Normal lungs and lung fibroblasts expressed renin, which was strongly upregulated in IPF lungs and fibroblasts (∼10-fold increase; p<0.05). Immunocytochemistry showed intense renin staining in IPF fibroblasts. Renin-stimulated lung fibroblasts displayed an increase in the expression of TGF-β1 (mean ± sd 1.8 × 10(3) ± 0.2 × 10(3) versus 1.2 × 10(3)± 0.3 × 10(3) mRNA copies per 18S ribosomal RNA; p<0.01) and collagen (5.93 × 10(2)± 0.66 × 10(2) versus 3.28 × 10(2) ± 0.5 × 10(2); p<0.01), while knocking down renin expression using siRNA provoked a strong decrease of both molecules. These effects were independent of Ang II, since neither losartan nor captopril decreased these effects. Renin also decreased matrix metalloprotease-1 expression and induced TGF-β1 activation (163 ± 34 versus 110 ± 15 pg active TGF-β1 per mg total protein). These findings highlight the possible role of renin as an Ang II-independent profibrotic factor in lung fibrosis.

PMID:
21659414
DOI:
10.1183/09031936.00130310
[Indexed for MEDLINE]
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