Shao Jie, Xia Zhen-wei, Li Yun-zhu, Yu Shan-chang, Deng Wei-wu
Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University Medical College, Shanghai 200025, China.
Zhonghua Er Ke Za Zhi. 2006 Jul;44(7):531-4.
Bronchial asthma is a chronic inflammatory disorder. Long-term inflammation leads to varying degrees of structural changes in the airway wall known as airway reconstruction or remodeling. These structural changes are found in the airways of most patients with prolonged disease. After remodeling, the airway walls show the submucous membrane becomes thick with collagen deposition, and the smooth muscle cells show hyperplasia and hypertrophy. Smooth muscle cells are a vital component of the airway wall, and a major effector cell involved in the course of bronchial contraction. Smooth muscle cell hyperplasia and hypertrophy are important pathological changes in airway remodeling. This study investigated the expression of markers of human airway smooth muscle cells (ASMCs) phenotypic change, which were matrix Gla protein (MGP) and major fibrosis proteins, after in vitro treatment with transforming growth factor-beta(1) (TGF-beta(1)).
Human ASMCs were subjected to primary culture in vitro. Ten groups of cells were treated with 100 microg/ml of TGF-beta(1), while the cells in the control groups were treated with 10% fetal bovine serum. After being cultured for 7 d, the cells of both groups were harvested. MGP mRNA expression was detected by RT-PCR. Protein levels of collagen I, III and V were determined by Western blot analysis.
Treated with TGF-beta(1), airway smooth muscle cells expressed MGP mRNA greater than controls [(62.3 +/- 13.1)% vs (27.4 +/- 11.4)%, P < 0.01]. Also, airway smooth muscle cells stimulated by TGF-beta(1) produced more collagen I, III and V than the control group (P < 0.01).
TGF-beta(1) induced expression of collagen III and V, which are early markers of the switch from a contractile to a synthetic phenotype in ASMCs. This induction is an indication that ASMCs have the potential to make this switch and that TGF-beta(1) is involved in airway remodeling.
支气管哮喘是一种慢性炎症性疾病。长期炎症会导致气道壁出现不同程度的结构变化，即气道重构。这些结构变化在大多数病程较长的患者气道中均可发现。重构后，气道壁表现为黏膜下层因胶原蛋白沉积而增厚，平滑肌细胞出现增生和肥大。平滑肌细胞是气道壁的重要组成部分，也是参与支气管收缩过程的主要效应细胞。平滑肌细胞增生和肥大是气道重构的重要病理变化。本研究调查了转化生长因子-β(1)（TGF-β(1)）体外处理后人气道平滑肌细胞（ASMCs）表型变化标志物，即基质Gla蛋白（MGP）和主要纤维化蛋白的表达情况。
人ASMCs进行体外原代培养。十组细胞用100μg/ml的TGF-β(1)处理，而对照组细胞用10%胎牛血清处理。培养7天后，收集两组细胞。通过RT-PCR检测MGP mRNA表达。采用蛋白质印迹分析测定I、III和V型胶原蛋白的蛋白水平。
用TGF-β(1)处理后，气道平滑肌细胞MGP mRNA表达高于对照组[（62.3±13.1）%对（27.4±11.4）%，P<0.01]。此外，TGF-β(1)刺激的气道平滑肌细胞产生的I、III和V型胶原蛋白比对照组更多（P<0.01）。
TGF-β(1)诱导了III和V型胶原蛋白的表达，这是ASMCs从收缩表型向合成表型转变的早期标志物。这种诱导表明ASMCs有发生这种转变的潜力，且TGF-β(1)参与了气道重构。
