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Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells

BACKGROUND: Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock pr...

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Autores principales: Hisatomi, Keiko, Mukae, Hiroshi, Sakamoto, Noriho, Ishimatsu, Yuji, Kakugawa, Tomoyuki, Hara, Shintaro, Fujita, Hanako, Nakamichi, Seiko, Oku, Hisashi, Urata, Yoshishige, Kubota, Hiroshi, Nagata, Kazuhiro, Kohno, Shigeru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403980/
https://www.ncbi.nlm.nih.gov/pubmed/22694981
http://dx.doi.org/10.1186/1471-2466-12-24
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author Hisatomi, Keiko
Mukae, Hiroshi
Sakamoto, Noriho
Ishimatsu, Yuji
Kakugawa, Tomoyuki
Hara, Shintaro
Fujita, Hanako
Nakamichi, Seiko
Oku, Hisashi
Urata, Yoshishige
Kubota, Hiroshi
Nagata, Kazuhiro
Kohno, Shigeru
author_facet Hisatomi, Keiko
Mukae, Hiroshi
Sakamoto, Noriho
Ishimatsu, Yuji
Kakugawa, Tomoyuki
Hara, Shintaro
Fujita, Hanako
Nakamichi, Seiko
Oku, Hisashi
Urata, Yoshishige
Kubota, Hiroshi
Nagata, Kazuhiro
Kohno, Shigeru
author_sort Hisatomi, Keiko
collection PubMed
description BACKGROUND: Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP) 47, a collagen-specific molecular chaperone, in human lung fibroblasts stimulated with transforming growth factor (TGF)-β1 in vitro. The increased numbers of HSP47-positive type II pneumocytes as well as fibroblasts were also diminished by pirfenidone in an animal model of pulmonary fibrosis induced by bleomycin. The present study evaluates the effects of pirfenidone on collagen type I and HSP47 expression in the human alveolar epithelial cell line, A549 cells in vitro. METHODS: The expression of collagen type I, HSP47 and E-cadherin mRNAs in A549 cells stimulated with TGF-β1 was evaluated by Northern blotting or real-time PCR. The expression of collagen type I, HSP47 and fibronectin proteins was assessed by immunocytochemical staining. RESULTS: TGF-β1 stimulated collagen type I and HSP47 mRNA and protein expression in A549 cells, and pirfenidone significantly inhibited this process. Pirfenidone also inhibited over-expression of the fibroblast phenotypic marker fibronectin in A549 cells induced by TGF-β1. CONCLUSION: We concluded that the anti-fibrotic effects of pirfenidone might be mediated not only through the direct inhibition of collagen type I expression but also through the inhibition of HSP47 expression in alveolar epithelial cells, which results in reduced collagen synthesis in lung fibrosis. Furthermore, pirfenidone might partially inhibit the epithelial-mesenchymal transition.
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spelling pubmed-34039802012-07-25 Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells Hisatomi, Keiko Mukae, Hiroshi Sakamoto, Noriho Ishimatsu, Yuji Kakugawa, Tomoyuki Hara, Shintaro Fujita, Hanako Nakamichi, Seiko Oku, Hisashi Urata, Yoshishige Kubota, Hiroshi Nagata, Kazuhiro Kohno, Shigeru BMC Pulm Med Research Article BACKGROUND: Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP) 47, a collagen-specific molecular chaperone, in human lung fibroblasts stimulated with transforming growth factor (TGF)-β1 in vitro. The increased numbers of HSP47-positive type II pneumocytes as well as fibroblasts were also diminished by pirfenidone in an animal model of pulmonary fibrosis induced by bleomycin. The present study evaluates the effects of pirfenidone on collagen type I and HSP47 expression in the human alveolar epithelial cell line, A549 cells in vitro. METHODS: The expression of collagen type I, HSP47 and E-cadherin mRNAs in A549 cells stimulated with TGF-β1 was evaluated by Northern blotting or real-time PCR. The expression of collagen type I, HSP47 and fibronectin proteins was assessed by immunocytochemical staining. RESULTS: TGF-β1 stimulated collagen type I and HSP47 mRNA and protein expression in A549 cells, and pirfenidone significantly inhibited this process. Pirfenidone also inhibited over-expression of the fibroblast phenotypic marker fibronectin in A549 cells induced by TGF-β1. CONCLUSION: We concluded that the anti-fibrotic effects of pirfenidone might be mediated not only through the direct inhibition of collagen type I expression but also through the inhibition of HSP47 expression in alveolar epithelial cells, which results in reduced collagen synthesis in lung fibrosis. Furthermore, pirfenidone might partially inhibit the epithelial-mesenchymal transition. BioMed Central 2012-06-13 /pmc/articles/PMC3403980/ /pubmed/22694981 http://dx.doi.org/10.1186/1471-2466-12-24 Text en Copyright ©2012 Hisatomi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hisatomi, Keiko
Mukae, Hiroshi
Sakamoto, Noriho
Ishimatsu, Yuji
Kakugawa, Tomoyuki
Hara, Shintaro
Fujita, Hanako
Nakamichi, Seiko
Oku, Hisashi
Urata, Yoshishige
Kubota, Hiroshi
Nagata, Kazuhiro
Kohno, Shigeru
Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells
title Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells
title_full Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells
title_fullStr Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells
title_full_unstemmed Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells
title_short Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells
title_sort pirfenidone inhibits tgf-β1-induced over-expression of collagen type i and heat shock protein 47 in a549 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403980/
https://www.ncbi.nlm.nih.gov/pubmed/22694981
http://dx.doi.org/10.1186/1471-2466-12-24
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