Department of Pharmacology, Uniformed Services University of Health Sciences, Bethesda, MD 20852, USA.
Acta Pharmacol Sin. 2011 Jan;32(1):12-20. doi: 10.1038/aps.2010.90. Epub 2010 Dec 6.
Pulmonary remodeling is characterized by the permanent and progressive loss of the normal alveolar architecture, especially the loss of alveolar epithelial and endothelial cells, persistent proliferation of activated fibroblasts, or myofibroblasts, and alteration of extracellular matrix. Hepatocyte growth factor (HGF) is a pleiotropic factor, which induces cellular motility, survival, proliferation, and morphogenesis, depending upon the cell type. In the adult, HGF has been demonstrated to play a critical role in tissue repair, including in the lung. Administration of HGF protein or ectopic expression of HGF has been demonstrated in animal models of pulmonary fibrosis to induce normal tissue repair and to prevent fibrotic remodeling. HGF-induced inhibition of fibrotic remodeling may occur via multiple direct and indirect mechanisms including the induction of cell survival and proliferation of pulmonary epithelial and endothelial cells, and the reduction of myofibroblast accumulation.
肺重构的特征是正常肺泡结构的永久性和进行性丧失，特别是肺泡上皮细胞和内皮细胞的丧失，活化的成纤维细胞或肌成纤维细胞的持续增殖，以及细胞外基质的改变。肝细胞生长因子（HGF）是一种多效性因子，根据细胞类型的不同，它可诱导细胞的运动性、存活、增殖和形态发生。在成人中，HGF 已被证明在组织修复中发挥关键作用，包括在肺部。在肺纤维化的动物模型中，给予 HGF 蛋白或异位表达 HGF 已被证明可诱导正常组织修复并预防纤维性重塑。HGF 诱导的抗纤维化重塑可能通过多种直接和间接机制发生，包括诱导肺上皮细胞和内皮细胞的存活和增殖，以及减少肌成纤维细胞的聚集。
