CTGF公司
纤维化
肺纤维化
结缔组织
转化生长因子
下调和上调
特发性肺纤维化
医学
肺
细胞外基质
生长因子
病理
肌成纤维细胞
癌症研究
生物
内分泌学
内科学
细胞生物学
受体
基因
生物化学
作者
Toyoshi Yanagihara,Sy Giin Chong,Mahsa Gholiof,Kenneth E. Lipson,Quan Zhou,Ciaran Scallan,Chandak Upagupta,Jussi Tikkanen,S. Keshavjee,Kjetil Ask,Martin Kolb
标识
DOI:10.1101/2020.07.04.187492
摘要
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive and excessive accumulation of myofibroblasts and extracellular matrix in the lung. Connective-tissue growth factor (CTGF) is known to exacerbate pulmonary fibrosis in radiation-induced lung fibrosis, and in this study, we show the upregulation of CTGF from a rat lung fibrosis model induced by adenovirus vector encoding active TGF-β1 (AdTGF-β1), and also in patients with IPF. The expression of CTGF was upregulated in vascular smooth muscle cells cultured from fibrotic lungs on days 7 or 14 as well as endothelial cells sorted from fibrotic lungs on day 14 or 28 respectively. These findings suggest the role of different cells in maintaining the fibrotic phenotype during fibrogenesis. Treatment of fibroblasts with recombinant CTGF along with TGF-β increases pro-fibrotic markers in fibroblasts, confirming the synergistic effect of recombinant CTGF with TGF-β in inducing pulmonary fibrosis. Also, fibrotic extracellular matrix upregulated the expression of CTGF, as compared to normal extracellular matrix, suggesting that not only profibrotic mediators but also a profibrotic environment contributes to fibrogenesis. We also showed that pamrevlumab, a CTGF inhibitory antibody, partially attenuates fibrosis in the model. These results suggest that pamrevlumab could be an option for the treatment of pulmonary fibrosis.
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