Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway

Abstract To investigate the potential role of vitamin D (1,25(OH)2D3) in preventing the development of nasal polyps, we examined the effect of vitamin D on myofibroblast differentiation and extracellular matrix (ECM) production in TGF-β1-induced nasal polyp-derived fibroblasts (NPDFs) and elucidated...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Seoung-Ae Lee, Hyun-Woo Yang, Ji-Young Um, Jae-Min Shin, Il-Ho Park, Heung-Man Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/11559d6f25224c8a808047db444ec411
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:11559d6f25224c8a808047db444ec411
record_format	dspace
spelling	oai:doaj.org-article:11559d6f25224c8a808047db444ec4112021-12-02T15:06:17ZVitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway10.1038/s41598-017-07561-62045-2322https://doaj.org/article/11559d6f25224c8a808047db444ec4112017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07561-6https://doaj.org/toc/2045-2322Abstract To investigate the potential role of vitamin D (1,25(OH)2D3) in preventing the development of nasal polyps, we examined the effect of vitamin D on myofibroblast differentiation and extracellular matrix (ECM) production in TGF-β1-induced nasal polyp-derived fibroblasts (NPDFs) and elucidated the mechanisms underlying its inhibitory effect. 1,25(OH)2D3 significantly reduced expression levels of α-SMA, a myofibroblast marker, and fibronectin, a representative ECM component, in a dose-dependent manner in TGF-β1-induced NPDFs. 1,25(OH)2D3 suppressed activated Smad2/3 in time-course. Up-regulation of α-SMA, fibronectin and phosphorylation of Smad2/3 by TGF-β1 was unaffected by 1,25(OH)2D3 in NPDFs after vitamin D receptor-specific siRNA transfection. We confirmed that the Smad2/3-specific inhibitor SIS3 inactivated Smad2/3 and reduced α-SMA and fibronectin expression. Furthermore, acetylation of histone H3 was compromised by 1,25(OH)2D3, leading to inhibition of collagen 1A1, collagen 1A2 and α-SMA gene expression. Treatment with 1,25(OH)2D3 also significantly suppressed TGF-β1-enhanced contractility and motility in a contraction assay and Transwell migration assay. Finally, 1,25(OH)2D3 had a similar effect in ex vivo organ cultures of nasal polyps. Taken together, our results suggest that 1,25(OH)2D3 might be an effective therapy for nasal polyps by reducing myofibroblast differentiation and ECM production mediated by Smad2/3-dependent TGF-β1 signaling pathways in NPDFs.Seoung-Ae LeeHyun-Woo YangJi-Young UmJae-Min ShinIl-Ho ParkHeung-Man LeeNature 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 Seoung-Ae Lee Hyun-Woo Yang Ji-Young Um Jae-Min Shin Il-Ho Park Heung-Man Lee Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway
description	Abstract To investigate the potential role of vitamin D (1,25(OH)2D3) in preventing the development of nasal polyps, we examined the effect of vitamin D on myofibroblast differentiation and extracellular matrix (ECM) production in TGF-β1-induced nasal polyp-derived fibroblasts (NPDFs) and elucidated the mechanisms underlying its inhibitory effect. 1,25(OH)2D3 significantly reduced expression levels of α-SMA, a myofibroblast marker, and fibronectin, a representative ECM component, in a dose-dependent manner in TGF-β1-induced NPDFs. 1,25(OH)2D3 suppressed activated Smad2/3 in time-course. Up-regulation of α-SMA, fibronectin and phosphorylation of Smad2/3 by TGF-β1 was unaffected by 1,25(OH)2D3 in NPDFs after vitamin D receptor-specific siRNA transfection. We confirmed that the Smad2/3-specific inhibitor SIS3 inactivated Smad2/3 and reduced α-SMA and fibronectin expression. Furthermore, acetylation of histone H3 was compromised by 1,25(OH)2D3, leading to inhibition of collagen 1A1, collagen 1A2 and α-SMA gene expression. Treatment with 1,25(OH)2D3 also significantly suppressed TGF-β1-enhanced contractility and motility in a contraction assay and Transwell migration assay. Finally, 1,25(OH)2D3 had a similar effect in ex vivo organ cultures of nasal polyps. Taken together, our results suggest that 1,25(OH)2D3 might be an effective therapy for nasal polyps by reducing myofibroblast differentiation and ECM production mediated by Smad2/3-dependent TGF-β1 signaling pathways in NPDFs.
format	article
author	Seoung-Ae Lee Hyun-Woo Yang Ji-Young Um Jae-Min Shin Il-Ho Park Heung-Man Lee
author_facet	Seoung-Ae Lee Hyun-Woo Yang Ji-Young Um Jae-Min Shin Il-Ho Park Heung-Man Lee
author_sort	Seoung-Ae Lee
title	Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway
title_short	Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway
title_full	Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway
title_fullStr	Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway
title_full_unstemmed	Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway
title_sort	vitamin d attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/11559d6f25224c8a808047db444ec411
work_keys_str_mv	AT seoungaelee vitamindattenuatesmyofibroblastdifferentiationandextracellularmatrixaccumulationinnasalpolypderivedfibroblaststhroughsmad23signalingpathway AT hyunwooyang vitamindattenuatesmyofibroblastdifferentiationandextracellularmatrixaccumulationinnasalpolypderivedfibroblaststhroughsmad23signalingpathway AT jiyoungum vitamindattenuatesmyofibroblastdifferentiationandextracellularmatrixaccumulationinnasalpolypderivedfibroblaststhroughsmad23signalingpathway AT jaeminshin vitamindattenuatesmyofibroblastdifferentiationandextracellularmatrixaccumulationinnasalpolypderivedfibroblaststhroughsmad23signalingpathway AT ilhopark vitamindattenuatesmyofibroblastdifferentiationandextracellularmatrixaccumulationinnasalpolypderivedfibroblaststhroughsmad23signalingpathway AT heungmanlee vitamindattenuatesmyofibroblastdifferentiationandextracellularmatrixaccumulationinnasalpolypderivedfibroblaststhroughsmad23signalingpathway
_version_	1718388496377315328

Vitamin D attenuates myofibroblast differentiation and extracellular matrix accumulation in nasal polyp-derived fibroblasts through smad2/3 signaling pathway

Ejemplares similares