PT  - JOURNAL ARTICLE
AU  - E. Montes
AU  - V. Ruiz
AU  - M. Checa
AU  - V. Maldonado
AU  - J.M. Zajgla
AU  - M. Montaño
AU  - R.O. Razo
AU  - J. Cisneros
AU  - C. García-de-Alba
AU  - A. Pardo
AU  - M. Selman
TI  - Renin is an angiotensin-independent profibrotic mediator. Role in pulmonary fibrosis
AID  - 10.1183/09031936.00130310
DP  - 2011 Jan 01
TA  - European Respiratory Journal
PG  - erj01303-2010
4099  - http://erj.ersjournals.com/content/early/2011/06/09/09031936.00130310.short
4100  - http://erj.ersjournals.com/content/early/2011/06/09/09031936.00130310.full
AB  - The pathogenesis of idiopathic pulmonary fibrosis (IPF) is likely the result of interplay between cytokines/chemokines and growth factors. The renin-angiotensin system is involved, although its profibrotic effect is attributed to angiotensin 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 (NHLF) were stimulated with renin or transfected with renin-siRNA, and the expression of TGF-β1 and β1-type I collagen was analysed.Normal lungs and NHLF expressed renin which was strongly up-regulated in IPF lungs and fibroblasts (∼10-fold increase; p<0.05). Immunocytochemistry showed intense renin staining in IPF fibroblasts. Renin stimulated NHLF displayed an increase in the expression of TGF-β1(1.8±0.2×103 versus 1.2±0.3×103 mRNA/rR18s; p<0.01) and collagen (5.93±0.66×102 versus 3.28±0.5×102 mRNA/rR18s; p<0.01), while knocking-down renin expression by siRNA provoked a strong decrease of both molecules. These effects were independent of angiotensin II since neither losartan nor captopril decreased these effects. Renin also decreased MMP-1 expression and induced TGFβ1 activation (163±34 versus 110±15 pg active TGFβ1·mg−1 of total protein).These findings highlight the possible role of renin as an angiotensin-II-independent profibrotic factor in lung fibrosis.