Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. Despite the recent advances in the pathogenesis and treatment of SSc, effective therapies for fibrosis caused by SSc have not yet been established. In this study, we investigated the p...

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Autores principales:	Jong Seong Roh, Hoim Jeong, Beomgu Lee, Byung Wook Song, Seung Jin Han, Dong Hyun Sohn, Seung-Geun Lee
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	fibrosis systemic sclerosis mirodenafil cyclic guanosine monophosphate Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b25c890c26c74319ad7c9225e9a713c6
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spelling	oai:doaj.org-article:b25c890c26c74319ad7c9225e9a713c62021-11-11T14:23:42ZMirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis1976-83542151-248510.1080/19768354.2021.1995486https://doaj.org/article/b25c890c26c74319ad7c9225e9a713c62021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/19768354.2021.1995486https://doaj.org/toc/1976-8354https://doaj.org/toc/2151-2485Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. Despite the recent advances in the pathogenesis and treatment of SSc, effective therapies for fibrosis caused by SSc have not yet been established. In this study, we investigated the potential role of mirodenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, in the treatment of fibrosis in SSc. We used a bleomycin (BLM)-induced SSc mouse model to mimic the typical features of fibrosis in human SSc and examined the dermal thickness to assess the degree of skin fibrosis after staining with hematoxylin and eosin or Masson’s trichrome stains. The effect of mirodenafil on the expression of profibrotic genes was also analyzed by treating fibroblasts with transforming growth factor (TGF)-β and mirodenafil. We showed that mirodenafil ameliorated dermal fibrosis and downregulated the protein levels of fibrosis markers including COL1A1 and α-SMA in the BLM-induced SSc mouse model. Further, using mouse embryonic fibroblasts and human lung fibroblasts, we demonstrated that the expression of collagen and profibrotic genes was reduced by treatment with mirodenafil. Finally, we showed that mirodenafil inhibited TGF-β-induced phosphorylation of Smad2/3 in fibroblasts, which suggested that this drug may ameliorate fibrosis by suppressing the TGF-β/Smad signaling pathway. Our findings suggest that mirodenafil possesses a therapeutic potential for treating fibrosis in SSc.Jong Seong RohHoim JeongBeomgu LeeByung Wook SongSeung Jin HanDong Hyun SohnSeung-Geun LeeTaylor & Francis Grouparticlefibrosissystemic sclerosismirodenafilcyclic guanosine monophosphateMedicine (General)R5-920Biology (General)QH301-705.5ENAnimal Cells and Systems, Vol 0, Iss 0, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fibrosis systemic sclerosis mirodenafil cyclic guanosine monophosphate Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	fibrosis systemic sclerosis mirodenafil cyclic guanosine monophosphate Medicine (General) R5-920 Biology (General) QH301-705.5 Jong Seong Roh Hoim Jeong Beomgu Lee Byung Wook Song Seung Jin Han Dong Hyun Sohn Seung-Geun Lee Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
description	Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. Despite the recent advances in the pathogenesis and treatment of SSc, effective therapies for fibrosis caused by SSc have not yet been established. In this study, we investigated the potential role of mirodenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, in the treatment of fibrosis in SSc. We used a bleomycin (BLM)-induced SSc mouse model to mimic the typical features of fibrosis in human SSc and examined the dermal thickness to assess the degree of skin fibrosis after staining with hematoxylin and eosin or Masson’s trichrome stains. The effect of mirodenafil on the expression of profibrotic genes was also analyzed by treating fibroblasts with transforming growth factor (TGF)-β and mirodenafil. We showed that mirodenafil ameliorated dermal fibrosis and downregulated the protein levels of fibrosis markers including COL1A1 and α-SMA in the BLM-induced SSc mouse model. Further, using mouse embryonic fibroblasts and human lung fibroblasts, we demonstrated that the expression of collagen and profibrotic genes was reduced by treatment with mirodenafil. Finally, we showed that mirodenafil inhibited TGF-β-induced phosphorylation of Smad2/3 in fibroblasts, which suggested that this drug may ameliorate fibrosis by suppressing the TGF-β/Smad signaling pathway. Our findings suggest that mirodenafil possesses a therapeutic potential for treating fibrosis in SSc.
format	article
author	Jong Seong Roh Hoim Jeong Beomgu Lee Byung Wook Song Seung Jin Han Dong Hyun Sohn Seung-Geun Lee
author_facet	Jong Seong Roh Hoim Jeong Beomgu Lee Byung Wook Song Seung Jin Han Dong Hyun Sohn Seung-Geun Lee
author_sort	Jong Seong Roh
title	Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
title_short	Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
title_full	Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
title_fullStr	Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
title_full_unstemmed	Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
title_sort	mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/b25c890c26c74319ad7c9225e9a713c6
work_keys_str_mv	AT jongseongroh mirodenafilamelioratesskinfibrosisinbleomycininducedmousemodelofsystemicsclerosis AT hoimjeong mirodenafilamelioratesskinfibrosisinbleomycininducedmousemodelofsystemicsclerosis AT beomgulee mirodenafilamelioratesskinfibrosisinbleomycininducedmousemodelofsystemicsclerosis AT byungwooksong mirodenafilamelioratesskinfibrosisinbleomycininducedmousemodelofsystemicsclerosis AT seungjinhan mirodenafilamelioratesskinfibrosisinbleomycininducedmousemodelofsystemicsclerosis AT donghyunsohn mirodenafilamelioratesskinfibrosisinbleomycininducedmousemodelofsystemicsclerosis AT seunggeunlee mirodenafilamelioratesskinfibrosisinbleomycininducedmousemodelofsystemicsclerosis
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Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis

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