Nottingham Respiratory Biomedical Research Unit, Nottingham University Hospitals, University of Nottingham, Hucknall Road, Nottingham, UK.
Proc Am Thorac Soc. 2012 Jul;9(3):130-6. doi: 10.1513/pats.201201-003AW.
Lung fibrosis can affect the parenchyma and the airways, classically giving rise to idiopathic pulmonary fibrosis (IPF) in the parenchyma or airway remodeling in asthma and chronic obstructive pulmonary disease. TGF-β activation has been implicated in the fibrosis of both IPF and airway remodeling. However, the mechanisms of TGF-β activation appear to differ depending on the cellular and anatomical compartments, with implications on disease pathogenesis. Although it appears that epithelial cell activation of TGF-β by the αvβ6 integrin is central in IPF, mesenchymal activation of TGF-β by the αvβ5 and αvβ8 integrins appears to predominate in airway remodeling. Interestingly, the mechanism of TGF-β by the integrins αvβ6 and αvβ5 is shared, relying on cytoskeletal changes, whereas activation of TGF-β by the αvβ8 integrin is distinct, relying on proteolytic cleavage of the latency-associated peptide of TGF-β by matrix metalloproteinase 14. This article describes the mechanisms through which epithelial cells activate TGF-β by the αvβ6 integrin and mesenchymal cells activate TGF-β by the αvβ5 integrin, and highlights their roles in lung fibrosis.
肺纤维化可影响实质和气道，经典地导致特发性肺纤维化（IPF）中的实质纤维化或哮喘和慢性阻塞性肺疾病中的气道重塑。TGF-β 的激活与 IPF 和气道重塑的纤维化都有关。然而，TGF-β 的激活机制似乎因细胞和解剖隔室而异，对疾病发病机制有影响。尽管似乎上皮细胞通过αvβ6 整联蛋白激活 TGF-β 在 IPF 中起核心作用，但间质细胞通过αvβ5 和αvβ8 整联蛋白激活 TGF-β似乎在气道重塑中占主导地位。有趣的是，整联蛋白αvβ6 和αvβ5 激活 TGF-β 的机制是共享的，依赖于细胞骨架的变化，而αvβ8 整联蛋白激活 TGF-β则不同，依赖于基质金属蛋白酶 14 对 TGF-β 潜伏相关肽的蛋白水解切割。本文描述了上皮细胞通过αvβ6 整联蛋白激活 TGF-β和间质细胞通过αvβ5 整联蛋白激活 TGF-β的机制，并强调了它们在肺纤维化中的作用。
