title: Zinc supplementation suppresses the progression of bile duct ligation-induced liver fibrosis in mice.
abstract: Metallothionein (MT) gene therapy leads to resolution of liver fibrosis in mouse model, in which the activation of collagenases is involved in the regression of liver fibrosis. MT plays a critical role in zinc sequestration in the liver suggesting its therapeutic effect would be mediated by zinc. The present study was undertaken to test the hypothesis that zinc supplementation suppresses liver fibrosis. Male Kunming mice subjected to bile duct ligation (BDL) resulted in liver fibrosis as assessed by increased α-smooth muscle actin (α-SMA) and collagen I production/deposition in the liver. Zinc supplementation was introduced 4 weeks after BDL surgery via intragastric administration once daily for 2 weeks resulting in a significant reduction in the collagen deposition in the liver and an increase in the survival rate. Furthermore, zinc suppressed gene expression of α-SMA and collagen I and enhanced the capacity of collagen degradation, as determined by the increased activity of total collagenases and elevated mRNA and protein levels of MMP13. Therefore, the results demonstrate that zinc supplementation suppresses BDL-induced liver fibrosis through both inhibiting collagen production and enhancing collagen degradation.
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Shi
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Sheng
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xu
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Huang
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA yjkang01@louisville.edu.
authors.forename: Y James
authors.initials: YJ
authors.lastname: Kang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D015032:Zinc / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D012333:RNA, Messenger; C544013:alpha-smooth muscle actin, mouse; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D015032:Zinc
keywords: Kunming mice; Zinc; bile duct ligation; collagenases; liver fibrosis; metalloproteinases