Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Respir Physiol Neurobiol. 2011 Aug 15;177(3):236-40. doi: 10.1016/j.resp.2011.04.019. Epub 2011 Apr 22.
Insufficiency of tissue repair by pulmonary fibroblasts may contribute to the decrease in elastic fibres in chronic obstructive pulmonary disease (COPD). In this study, the repair function of COPD fibroblasts was assessed by examining the response to transforming growth factor (TGF)-β1. Primary pulmonary fibroblasts were cultured from lung tissue of COPD patients and smoking control subjects. Cellular proliferation was measured with Alamar Blue reduction method. Levels of tropoelastin mRNA and soluble elastin was measured using real-time RT-PCR and Fastin elastin assay respectively. The percentage of increase in proliferation and elastin production after TGF-β1 (1 ng/ml) treatment was calculated for fibroblasts from each subject. COPD fibroblasts showed slower proliferation than control fibroblasts, and a reduced response to TGF-β1 stimulation. The promotive effect of TGF-β1 on elastin synthesis in control fibroblasts was significantly diminished in fibroblasts from COPD patients. Our findings indicate that COPD lung fibroblasts have a significantly decreased response to TGF-β1 in terms of proliferation and elastin production.
肺成纤维细胞组织修复不足可能导致慢性阻塞性肺疾病(COPD)中弹性纤维减少。在这项研究中,通过检测转化生长因子(TGF)-β1 的反应来评估 COPD 成纤维细胞的修复功能。从 COPD 患者和吸烟对照者的肺组织中培养原代肺成纤维细胞。用 Alamar Blue 还原法测量细胞增殖。使用实时 RT-PCR 和 Fastin 弹性蛋白测定法分别测量原肌球蛋白 mRNA 和可溶性弹性蛋白的水平。计算每个受试者的 TGF-β1(1ng/ml)处理后增殖和弹性蛋白产生的百分比增加。与对照成纤维细胞相比,COPD 成纤维细胞的增殖较慢,对 TGF-β1 刺激的反应减弱。COPD 患者成纤维细胞中 TGF-β1 对弹性蛋白合成的促进作用明显减弱。我们的研究结果表明,COPD 肺成纤维细胞在增殖和弹性蛋白产生方面对 TGF-β1 的反应明显降低。