Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung

Abstract Idiopathic pulmonary fibrosis (IPF) is a severe disorder leading to progressive and irreversible loss of pulmonary function. In this study we investigated the anti-fibrotic effect of vitamin D using a mouse model of IPF. Lung fibrosis was induced with bleomycin in vitamin D-sufficient and v...

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Autores principales:	Jianjun Chang, Hongguang Nie, Xin Ge, Jie Du, Weicheng Liu, Xue Li, Yue Sun, Xinzhi Wei, Zhe Xun, Yan Chun Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b82009ba29f42d6a720d696b13be5a8
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spelling	oai:doaj.org-article:6b82009ba29f42d6a720d696b13be5a82021-12-02T15:10:50ZVitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung10.1038/s41598-021-96152-72045-2322https://doaj.org/article/6b82009ba29f42d6a720d696b13be5a82021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96152-7https://doaj.org/toc/2045-2322Abstract Idiopathic pulmonary fibrosis (IPF) is a severe disorder leading to progressive and irreversible loss of pulmonary function. In this study we investigated the anti-fibrotic effect of vitamin D using a mouse model of IPF. Lung fibrosis was induced with bleomycin in vitamin D-sufficient and vitamin D-deficient C57BL/6 mice. We found that treatment with active vitamin D analog paricalcitol prevented mouse body weight loss and alleviated lung fibrosis, whereas vitamin D deficiency severely aggravated lung injury. At the molecular level, paricalcitol treatment suppressed the induction of fibrotic inducer TGF-β and extracellular matrix proteins α-SMA, collagen type I and fibronectin in the lung, whereas vitamin D deficiency exacerbated the induction of these proteins. Interestingly, bleomycin treatment activated the local renin–angiotensin system (RAS) in the lung, manifested by the induction of renin, angiotensinogen, angiotensin II and angiotensin receptor type 1 (AT1R). Paricalcitol treatment suppressed the induction of these RAS components, whereas vitamin D deficiency enhanced the activation of the lung RAS. We also showed that treatment of bleomycin-induced vitamin D-deficient mice with AT1R antagonist losartan relieved weight loss, substantially ameliorated lung fibrosis and markedly blocked TGF-β induction in the lung. Moreover, we demonstrated that in lung fibroblast cultures, TGF-β and angiotensin II synergistically induced TGF-β, AT1R, α-SMA, collagen type I and fibronectin, whereas 1,25-dihydroxyvitamin D markedly suppressed the induction of these fibrotic markers. Collectively, these observations strongly suggest that vitamin D mitigates lung fibrosis by blocking the activation of the lung RAS in this mouse model of IPF.Jianjun ChangHongguang NieXin GeJie DuWeicheng LiuXue LiYue SunXinzhi WeiZhe XunYan Chun LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jianjun Chang Hongguang Nie Xin Ge Jie Du Weicheng Liu Xue Li Yue Sun Xinzhi Wei Zhe Xun Yan Chun Li Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
description	Abstract Idiopathic pulmonary fibrosis (IPF) is a severe disorder leading to progressive and irreversible loss of pulmonary function. In this study we investigated the anti-fibrotic effect of vitamin D using a mouse model of IPF. Lung fibrosis was induced with bleomycin in vitamin D-sufficient and vitamin D-deficient C57BL/6 mice. We found that treatment with active vitamin D analog paricalcitol prevented mouse body weight loss and alleviated lung fibrosis, whereas vitamin D deficiency severely aggravated lung injury. At the molecular level, paricalcitol treatment suppressed the induction of fibrotic inducer TGF-β and extracellular matrix proteins α-SMA, collagen type I and fibronectin in the lung, whereas vitamin D deficiency exacerbated the induction of these proteins. Interestingly, bleomycin treatment activated the local renin–angiotensin system (RAS) in the lung, manifested by the induction of renin, angiotensinogen, angiotensin II and angiotensin receptor type 1 (AT1R). Paricalcitol treatment suppressed the induction of these RAS components, whereas vitamin D deficiency enhanced the activation of the lung RAS. We also showed that treatment of bleomycin-induced vitamin D-deficient mice with AT1R antagonist losartan relieved weight loss, substantially ameliorated lung fibrosis and markedly blocked TGF-β induction in the lung. Moreover, we demonstrated that in lung fibroblast cultures, TGF-β and angiotensin II synergistically induced TGF-β, AT1R, α-SMA, collagen type I and fibronectin, whereas 1,25-dihydroxyvitamin D markedly suppressed the induction of these fibrotic markers. Collectively, these observations strongly suggest that vitamin D mitigates lung fibrosis by blocking the activation of the lung RAS in this mouse model of IPF.
format	article
author	Jianjun Chang Hongguang Nie Xin Ge Jie Du Weicheng Liu Xue Li Yue Sun Xinzhi Wei Zhe Xun Yan Chun Li
author_facet	Jianjun Chang Hongguang Nie Xin Ge Jie Du Weicheng Liu Xue Li Yue Sun Xinzhi Wei Zhe Xun Yan Chun Li
author_sort	Jianjun Chang
title	Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
title_short	Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
title_full	Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
title_fullStr	Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
title_full_unstemmed	Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
title_sort	vitamin d suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6b82009ba29f42d6a720d696b13be5a8
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Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung

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