Chronic Activation of the renin-angiotensin system induces lung fibrosis

Jiaolong Wang, Li Chen, Bohao Chen, Angelo Meliton, Shu Qian Liu, Yongyan Shi, Tianjing Liu, Dilip K. Deb, Julian Solway, Yan Chun Li*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Pulmonary fibrosis is a serious lung disorder that can lead to respiratory failure. Here we show that transgenic mice expressing active renin from the liver (RenTgMK) developed progressive pulmonary fibrosis leading to impaired pulmonary function. Histological analyses revealed a marked increase in extracellular matrix (ECM) deposition and decrease in alveolar size in the lungs of RenTgMK mice compared to wild-type (WT) littermates, accompanied with increased expression of ECM proteins and fibrogenic factors. The increase in lung fibrosis led to a substantial decrease in respiratory system compliance. Two-week treatment with aliskiren (renin inhibitor) or losartan (AT1 antagonist) ameliorated pulmonary ECM deposition, blocked the induction of ECM proteins and fibrogenic factors and improved respiratory compliance in RenTgMK mice, confirming a critical role of the renin-Ang II-AT1 cascade in promoting pulmonary fibrogenesis. However, when RenTgMK mice were treated with hydralazine (a smooth muscle relaxant), the blood pressure was normalized but the lung fibrotic abnormalities, fibrogenic gene induction and pulmonary elasticity were not corrected. Moreover, intratracheal instillation of lipopolysaccharide induced more severe lung injury in RenTgMK mice compared to WT littermates. These observations demonstrate that the renin-angiotensin system is a key mediator of lung fibrosis, and its pro-fibrotic effect is independent of blood pressure.

Original languageEnglish (US)
Article number15561
JournalScientific reports
Volume5
DOIs
StatePublished - Oct 23 2015

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Renin-Angiotensin System
Fibrosis
Lung
Renin
Pulmonary Fibrosis
Extracellular Matrix Proteins
Compliance
Extracellular Matrix
Blood Pressure
Hydralazine
Losartan
Elasticity
Lung Injury
Respiratory Insufficiency
Respiratory System
Transgenic Mice
Smooth Muscle
Lipopolysaccharides
Liver

ASJC Scopus subject areas

  • General

Cite this

Wang, J., Chen, L., Chen, B., Meliton, A., Liu, S. Q., Shi, Y., ... Chun Li, Y. (2015). Chronic Activation of the renin-angiotensin system induces lung fibrosis. Scientific reports, 5, [15561]. https://doi.org/10.1038/srep15561
Wang, Jiaolong ; Chen, Li ; Chen, Bohao ; Meliton, Angelo ; Liu, Shu Qian ; Shi, Yongyan ; Liu, Tianjing ; Deb, Dilip K. ; Solway, Julian ; Chun Li, Yan. / Chronic Activation of the renin-angiotensin system induces lung fibrosis. In: Scientific reports. 2015 ; Vol. 5.
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Wang, J, Chen, L, Chen, B, Meliton, A, Liu, SQ, Shi, Y, Liu, T, Deb, DK, Solway, J & Chun Li, Y 2015, 'Chronic Activation of the renin-angiotensin system induces lung fibrosis', Scientific reports, vol. 5, 15561. https://doi.org/10.1038/srep15561

Chronic Activation of the renin-angiotensin system induces lung fibrosis. / Wang, Jiaolong; Chen, Li; Chen, Bohao; Meliton, Angelo; Liu, Shu Qian; Shi, Yongyan; Liu, Tianjing; Deb, Dilip K.; Solway, Julian; Chun Li, Yan.

In: Scientific reports, Vol. 5, 15561, 23.10.2015.

Research output: Contribution to journalArticle

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AU - Meliton, Angelo

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AU - Deb, Dilip K.

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AU - Chun Li, Yan

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