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- Title
Geranylgeranyl diphosphate synthase deficiency aggravates lung fibrosis in mice by modulating TGF-β1/BMP-4 signaling.
- Authors
Meizi Chena; Bing Wana; Suhua Zhua; Fang Zhang; Jiajia Jin; Xinying Li; Xianghai Wang; Yanling Lv; Cen Chen; Tangfeng Lv; Yong Song
- Abstract
Geranylgeranyl diphosphate synthase (GGPPS) is an enzyme that catalyzes the synthesis of geranylgeranyl pyrophosphate (GGPP). GGPPS is implicated in many disorders, but its role in idiopathic pulmonary fibrosis (IPF) remains unclear. This study aimed to investigate the role of GGPPS in IPF. We established bleomycin-induced lung injury in a lung-specific GGPPS-deficient mouse (GGPPS−/−) and detected GGPPS expression in lung tissues by Western blot and immunohistochemistry analysis. We found that GGPPS expression increased during lung injury and fibrosis in mice induced by bleomycin, and GGPPS deficiency augmented lung fibrosis. GGPPS deficiency activated lung fibroblast by facilitating transforming growth factor β1 while antagonizing bone morphogenetic protein 4 signaling. Notably, the supplementation of exogenous GGPP mitigated lung fibrosis in GGPPS−/− mice induced by bleomycin. In conclusion, our findings suggest that GGPPS provides protection against pulmonary fibrosis and that the restoration of protein geranylgeranylation may benefit statin-induced lung injury.
- Subjects
PULMONARY fibrosis; IDIOPATHIC pulmonary fibrosis; BONE morphogenetic proteins; TRANSFORMING growth factors-beta; WESTERN immunoblotting; TRANSFORMING growth factors; THIAMIN pyrophosphate
- Publication
Biological Chemistry, 2019, Vol 400, Issue 11, p1617
- ISSN
1431-6730
- Publication type
Article
- DOI
10.1515/hsz-2019-0168