title: Spontaneous liver fibrosis induced by long term dietary vitamin D deficiency in adult mice is related to chronic inflammation and enhanced apoptosis.
abstract: Epidemiological studies have revealed an association between vitamin D deficiency and various chronic liver diseases. However, it is not known whether lack of vitamin D can induce spontaneous liver fibrosis in an animal model. To study this, mice were fed either a control diet or a vitamin D deficient diet (VDD diet). For the positive control, liver fibrosis was induced with carbon tetrachloride. Here we show, for the first time, that liver fibrosis spontaneously developed in mice fed the VDD diet. Long-term administration of a VDD diet resulted in necro-inflammation and liver fibrosis. Inflammatory mediators including tumor necrosis factor-α, interleulin-1, interleukin-6, Toll-like-receptor 4, and monocyte chemotactic protein-1 were up-regulated in the livers of the mice fed the VDD diet. Conversely, the expression of Th2/M2 markers such as IL-10, IL-13, arginase 1, and heme oxygenase-1 were down-regulated in the livers of mice fed the VDD diet. Transforming growth factor-β1 and matrix metalloproteinase 13, which are important for fibrosis, were induced in the livers of mice fed the VDD diet. Moreover, the VDD diet triggered apoptosis in the parenchymal cells, in agreement with the increased levels of Fas and FasL, and decreased Bcl2 and Bclx. Thus, long-term vitamin D deficiency can provoke chronic inflammation that can induce liver apoptosis, which consequently activates hepatic stellate cells to initiate liver fibrosis.
authors.affiliation: Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: Longdong
authors.initials: L
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Sujun
authors.initials: S
authors.lastname: Zheng
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D014808:Vitamin D Deficiency / Q000150:complications* / Q000378:metabolism* / Q000473:pathology
keywords: cellules hépatiques stellaires; cirrhose; cirrhosis; déficience en vitamine D; fibrose du foie; hepatic stellate cells; inflammation; liver fibrosis; vitamin D; vitamin D deficiency; vitamine D