Moir Lyn M, Burgess Janette K, Black Judith L
Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
J Allergy Clin Immunol. 2008 Apr;121(4):1034-9.e4. doi: 10.1016/j.jaci.2007.12.1159. Epub 2008 Feb 4.
Integrin receptors signal to and from the extracellular matrix. Altered expression of the integrin receptors, such as the fibronectin receptor alpha(5)beta(1), might be implicated in extracellular matrix accumulation in airway remodeling in asthma.
We examined the effect of TGF-beta stimulation on integrin alpha(5)beta(1) expression and the role of alpha(5)beta(1) in fibronectin deposition and proliferation.
Integrin subunit alpha(5) and beta(1) expression in airway smooth muscle (ASM) from subjects with and without asthma was examined by means of PCR and flow cytometry. The effect of blocking alpha(5)beta(1) receptor on ASM proliferation to FBS was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. Cells were stimulated with TGF-beta in the presence or absence of extracellular signal-regulated kinase, phosphoinositide-3 kinase, or p38 inhibitors and antibodies to the alpha(5) and beta(1) subunits. The effect of blocking alpha(5)beta(1) receptor on fibronectin deposition was assessed by means of immunocytochemistry.
Proliferation of ASM cells from asthmatic and nonasthmatic subjects was inhibited by blocking the fibronectin receptor subunit alpha(5)beta(1). TGF-beta-induced alpha(5)beta(1) was extracellular signal-regulated kinase dependent but not phosphoinositide-3 kinase or p38 dependent. Blockade of the alpha(5)beta(1) receptor inhibited TGF-beta-induced fibronectin matrix deposition.
Through its increased expression by the profibrotic stimulus TGF-beta, integrin alpha(5)beta(1) might be important in regulating fibronectin deposition.
整合素受体与细胞外基质之间存在双向信号传导。整合素受体（如纤连蛋白受体α(5)β(1)）表达的改变可能与哮喘气道重塑过程中细胞外基质的积聚有关。
我们研究了转化生长因子-β（TGF-β）刺激对整合素α(5)β(1)表达的影响，以及α(5)β(1)在纤连蛋白沉积和增殖中的作用。
采用聚合酶链反应（PCR）和流式细胞术检测哮喘患者和非哮喘患者气道平滑肌（ASM）中整合素亚基α(5)和β(1)的表达。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法评估阻断α(5)β(1)受体对ASM细胞对胎牛血清（FBS）增殖的影响。在存在或不存在细胞外信号调节激酶、磷脂酰肌醇-3激酶或p38抑制剂以及α(5)和β(1)亚基抗体的情况下，用TGF-β刺激细胞。通过免疫细胞化学评估阻断α(5)β(1)受体对纤连蛋白沉积的影响。
阻断纤连蛋白受体亚基α(5)β(1)可抑制哮喘患者和非哮喘患者ASM细胞的增殖。TGF-β诱导的α(5)β(1)表达依赖于细胞外信号调节激酶，而不依赖于磷脂酰肌醇-3激酶或p38。阻断α(5)β(1)受体可抑制TGF-β诱导的纤连蛋白基质沉积。
通过促纤维化刺激物TGF-β增加其表达，整合素α(5)β(1)可能在调节纤连蛋白沉积中起重要作用。
