Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system

• Published in: Scientific reports Vol. 7; no. 1; pp. 3312 - 10
• Main Authors: Shi, Yongyan, Liu, Tianjing, Yao, Li, Xing, Yujiao, Zhao, Xinyi, Fu, Jianhua, Xue, Xindong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.06.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 14/63; 38/1; 38/22; 38/77; 692/308/1426; 692/699/1785; 82/29; Amides - pharmacology; Amides - therapeutic use; Angiotensin; Animals; Blood pressure; Blood Pressure - drug effects; Chronic Disease; Extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Female; Fibrosis; Fumarates - pharmacology; Fumarates - therapeutic use; Humanities and Social Sciences; Hypertension; Losartan - pharmacology; Losartan - therapeutic use; Lung - metabolism; Lung - pathology; Lung diseases; Mice; multidisciplinary; Nutrient deficiency; Pulmonary fibrosis; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - etiology; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - physiopathology; Renin; Renin-Angiotensin System - drug effects; Respiratory function; Science; Science (multidisciplinary); Smooth muscle; Vitamin D; Vitamin D Deficiency - complications; Vitamin deficiency
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-03474-6

Pulmonary fibrosis, which influences lung function and exacerbates a patient’s condition, is the ultimate stage of many lung diseases. Vitamin D deficiency is associated with pulmonary fibrosis and impaired lung function, but the underlying mechanism has not yet been fully elucidated. Moreover, vitamin D deficiency may cause over-activation of the renin-angiotensin system (RAS), which aggravates extracellular matrix (ECM) deposition and lung fibrosis. This study aims to investigate the effect of chronic vitamin D deficiency on lung fibrosis in otherwise healthy mice and to explore the role of RAS in this process. Mice were depleted of vitamin D through diet control and were compared with healthy subjects. Chronic vitamin D deficiency destructs lung structures, impairs lung development and stimulates ECM deposition. RAS components are also found to increase. These effects seem to worsen with prolonged vitamin D deficiency. By giving RAS blockers, these changes can be largely rescued. However, a smooth muscle relaxant whose regulatory effect on blood pressure is independent of RAS does not show similar effects. This study demonstrated that chronic vitamin D deficiency may induce RAS activation, which subsequently stimulates the expression of profibrotic factors and activates the fibrotic cascade. This profibrotic effect of RAS is independent of elevated blood pressure.