Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

Abstract To investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with...

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Autores principales:	Song Sun, Menghua Xu, Peijun Zhuang, Gong Chen, Kuiran Dong, Rui Dong, Shan Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08b2b6c99e254be38f897a386792bfae
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spelling	oai:doaj.org-article:08b2b6c99e254be38f897a386792bfae2021-12-02T18:37:08ZEffect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia10.1038/s41598-021-99158-32045-2322https://doaj.org/article/08b2b6c99e254be38f897a386792bfae2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99158-3https://doaj.org/toc/2045-2322Abstract To investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.Song SunMenghua XuPeijun ZhuangGong ChenKuiran DongRui DongShan ZhengNature 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 Song Sun Menghua Xu Peijun Zhuang Gong Chen Kuiran Dong Rui Dong Shan Zheng Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia
description	Abstract To investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.
format	article
author	Song Sun Menghua Xu Peijun Zhuang Gong Chen Kuiran Dong Rui Dong Shan Zheng
author_facet	Song Sun Menghua Xu Peijun Zhuang Gong Chen Kuiran Dong Rui Dong Shan Zheng
author_sort	Song Sun
title	Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia
title_short	Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia
title_full	Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia
title_fullStr	Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia
title_full_unstemmed	Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia
title_sort	effect and mechanism of vitamin d activation disorder on liver fibrosis in biliary atresia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/08b2b6c99e254be38f897a386792bfae
work_keys_str_mv	AT songsun effectandmechanismofvitamindactivationdisorderonliverfibrosisinbiliaryatresia AT menghuaxu effectandmechanismofvitamindactivationdisorderonliverfibrosisinbiliaryatresia AT peijunzhuang effectandmechanismofvitamindactivationdisorderonliverfibrosisinbiliaryatresia AT gongchen effectandmechanismofvitamindactivationdisorderonliverfibrosisinbiliaryatresia AT kuirandong effectandmechanismofvitamindactivationdisorderonliverfibrosisinbiliaryatresia AT ruidong effectandmechanismofvitamindactivationdisorderonliverfibrosisinbiliaryatresia AT shanzheng effectandmechanismofvitamindactivationdisorderonliverfibrosisinbiliaryatresia
_version_	1718377780083687424

Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

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