DIGNA Biotech, Madrid, Spain.
Cytokine. 2011 Mar;53(3):327-33. doi: 10.1016/j.cyto.2010.11.019. Epub 2010 Dec 23.
Pulmonary fibrosis encompasses several respiratory diseases characterized by epithelial cell injury, inflammation and fibrosis. Transforming growth factor (TGF)-β1 is one of the main profibrogenic cytokines involved in the pathogenesis of lung fibrosis. It induces fibroblast differentiation into myofibroblasts, which produce high levels of collagen and concomitantly loss of lung elasticity and reduction of the respiratory function. In the present study, we have investigated the effects of P17 (a TGF-β inhibitor peptide) on IMR-90 lung fibroblast differentiation in vitro, as well as on the inhibition of the development of bleomycin-induced pulmonary fibrosis in mice. It was found that in IMR-90 cells, P17 inhibited TGF-β1-induced expression of connective tissue growth factor and α-smooth muscle actin. In vivo, treatment of mice with P17 2days after bleomycin administration decreased lung fibrosis, areas of myofibroblast-like cells and lymphocyte infiltrate. P17 also reduced mRNA expression of collagen type I, fibronectin and the fibronectin splice isoform EDA in the lung, and increased the expression of IFN-γ mRNA. Finally, therapeutic treatment with P17 in mice with already established fibrosis was able to significantly attenuate the progression of lung fibrosis. These results suggest that P17 may be useful in the treatment of pulmonary fibrosis.
肺纤维化包括几种以上皮细胞损伤、炎症和纤维化为特征的呼吸系统疾病。转化生长因子 (TGF)-β1 是参与肺纤维化发病机制的主要促纤维化细胞因子之一。它诱导成纤维细胞分化为肌成纤维细胞，后者产生高水平的胶原，同时丧失肺弹性和降低呼吸功能。在本研究中，我们研究了 P17（一种 TGF-β 抑制剂肽）对体外 IMR-90 肺成纤维细胞分化的影响，以及对博来霉素诱导的小鼠肺纤维化发展的抑制作用。结果发现，在 IMR-90 细胞中，P17 抑制 TGF-β1 诱导的结缔组织生长因子和α-平滑肌肌动蛋白的表达。在体内，博来霉素给药后 2 天用 P17 治疗可减少肺纤维化、肌成纤维细胞样细胞和淋巴细胞浸润区域。P17 还降低了肺中胶原 I、纤连蛋白和纤连蛋白剪接异构体 EDA 的 mRNA 表达，并增加了 IFN-γ mRNA 的表达。最后，在已经存在纤维化的小鼠中进行的治疗性治疗能够显著减轻肺纤维化的进展。这些结果表明，P17 可能对肺纤维化的治疗有用。
