期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 79, 期 3, 页码 268-278出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2015.06.008
关键词
Integrin alpha v; Transgenic mice; MMP-1
类别
资金
- Japanese Ministry of Education, Science, Sports and Culture
- Japanese Ministry of Health, Labour and Welfare
- Grants-in-Aid for Scientific Research [15K15299, 25293179] Funding Source: KAKEN
Background: Integrins, especially alpha v integrin (ITGAV), are thought to play central roles in tissue fibrosis and the pathogenesis of scleroderma. So far, skin phenotype of tissue-specific transgenic mice of ITGAV have not been investigated. Objective: To investigate the role of ITGAV in the skin fibrosis, we engineered transgenic mice that overexpress ITGAV in the fibroblasts under the control of the COL1A2 enhancer promoter. Methods: Protein or RNA expression was evaluated by real-time PCR, immunohistochemistry, immunoblotting and immunoprecipitation. Results: Dermal thickness and Masson's trichrome staining were decreased in ITGAV transgenic (Tg) mice compared with wild-type (WT) mice. Protein and mRNA levels of COL1A2, COL3A1, CTGF and integrin beta 3 were down-regulated in the skin of Tg mice. In addition, the cell proliferation of cultured dermal fibroblasts obtained from Tg mice skin was decreased compared to those of WT mice. FAK phosphorylation was reduced in fibroblasts cultured from Tg mice skin in comparison to WT mice fibroblasts. Integrin beta 3 siRNA inhibited FAK phosphorylation levels, while FAK inhibitor reduced the expression of collagens and CTGF in mice dermal fibroblasts. Conclusions: The down-regulation of collagen or CTGF by decreased integrin beta 3 and FAK phosphorylation may cause the dermal thinning in Tg mice. Lower CTGF may also result in reduced growth of Tg mice fibroblasts. Our hypothesis is that the balance between alpha and beta chain of integrins positively or negatively control collagen expression and dermal thickness. This study gave a new insight in the treatment of tissue fibrosis and scleroderma by balancing integrin expression. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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