Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice

Abstract Idiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced colla...

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Autores principales:	Ken-ichiro Tanaka, Tomomi Niino, Tomoaki Ishihara, Ayaka Takafuji, Takahiro Takayama, Yuki Kanda, Toshifumi Sugizaki, Fumiya Tamura, Shota Kurotsu, Masahiro Kawahara, Tohru Mizushima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e655d241e86147c782e24d9512684d35
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spelling	oai:doaj.org-article:e655d241e86147c782e24d9512684d352021-12-02T11:53:09ZProtective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice10.1038/s41598-017-03676-y2045-2322https://doaj.org/article/e655d241e86147c782e24d9512684d352017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03676-yhttps://doaj.org/toc/2045-2322Abstract Idiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced collagen production in cultured fibroblasts from medicines already in clinical use. We selected felodipine based on its extent of collagen production inhibition, clinical safety profile, and other pharmacological activity. Felodipine is a dihydropyridine Ca2+ channel blocker that has been used clinically to treat patients with high blood pressure. Felodipine suppressed collagen production within LL29 cells in the presence of TGF-β1, but not in its absence. Intratracheal administration of felodipine prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction. Felodipine also improved pulmonary fibrosis, as well as lung and respiratory function when administered after fibrosis development. Furthermore, administration of felodipine suppressed a bleomycin-induced increase in activated fibroblasts in the lung. We also found other dihydropyridine Ca2+ channel blockers (nifedipine and benidipine) inhibited collagen production in vitro and partially prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction in vivo. We propose that these Ca2+ channel blockers may be therapeutically beneficial for IPF patients.Ken-ichiro TanakaTomomi NiinoTomoaki IshiharaAyaka TakafujiTakahiro TakayamaYuki KandaToshifumi SugizakiFumiya TamuraShota KurotsuMasahiro KawaharaTohru MizushimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ken-ichiro Tanaka Tomomi Niino Tomoaki Ishihara Ayaka Takafuji Takahiro Takayama Yuki Kanda Toshifumi Sugizaki Fumiya Tamura Shota Kurotsu Masahiro Kawahara Tohru Mizushima Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
description	Abstract Idiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced collagen production in cultured fibroblasts from medicines already in clinical use. We selected felodipine based on its extent of collagen production inhibition, clinical safety profile, and other pharmacological activity. Felodipine is a dihydropyridine Ca2+ channel blocker that has been used clinically to treat patients with high blood pressure. Felodipine suppressed collagen production within LL29 cells in the presence of TGF-β1, but not in its absence. Intratracheal administration of felodipine prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction. Felodipine also improved pulmonary fibrosis, as well as lung and respiratory function when administered after fibrosis development. Furthermore, administration of felodipine suppressed a bleomycin-induced increase in activated fibroblasts in the lung. We also found other dihydropyridine Ca2+ channel blockers (nifedipine and benidipine) inhibited collagen production in vitro and partially prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction in vivo. We propose that these Ca2+ channel blockers may be therapeutically beneficial for IPF patients.
format	article
author	Ken-ichiro Tanaka Tomomi Niino Tomoaki Ishihara Ayaka Takafuji Takahiro Takayama Yuki Kanda Toshifumi Sugizaki Fumiya Tamura Shota Kurotsu Masahiro Kawahara Tohru Mizushima
author_facet	Ken-ichiro Tanaka Tomomi Niino Tomoaki Ishihara Ayaka Takafuji Takahiro Takayama Yuki Kanda Toshifumi Sugizaki Fumiya Tamura Shota Kurotsu Masahiro Kawahara Tohru Mizushima
author_sort	Ken-ichiro Tanaka
title	Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
title_short	Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
title_full	Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
title_fullStr	Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
title_full_unstemmed	Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
title_sort	protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e655d241e86147c782e24d9512684d35
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Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice

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