Sureshbabu A, Tonner E, Allan G J, Flint D J
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, SIPBS Building, 161 Cathedral Street, Glasgow G4 0RE, UK.
Pulm Med. 2011;2011:517687. doi: 10.1155/2011/517687. Epub 2011 Jan 26.
Although most evident in the skin, the process of scarring, or fibrosis, occurs in all major organs because of impaired epithelial self-renewal. No current therapy exists for Idiopathic pulmonary fibrosis. The major profibrotic factor is TGF-β1 and developing inhibitors is an area of active research. Recently, IGFBP-5 has also been identified as a profibrotic factor, and studies suggest that, while both TGF-β1 and IGFBP-5 activate mesenchymal cells to increase collagen and fibronectin production, their effects on epithelial cells are distinct. TGF-β1 induces cell death and/or EMT in the epithelial cells, exacerbating the disruption of tissue architecture. In contrast, IGFBP-5 induces epithelial cell spreading over collagen or fibronectin matrices, increases secretion of laminin, the epithelial basement membrane, and enhances the survival of epithelial cells in nutrient-poor conditions, as exists in scar tissue. Thus, IGFBP-5 may enhance repair and may be an important target for antifibrotic therapies.
尽管瘢痕形成（即纤维化）过程在皮肤中最为明显，但由于上皮自我更新受损，所有主要器官都会发生这一过程。目前尚无针对特发性肺纤维化的治疗方法。主要的促纤维化因子是转化生长因子-β1（TGF-β1），开发其抑制剂是一个活跃的研究领域。最近，胰岛素样生长因子结合蛋白-5（IGFBP-5）也被确定为一种促纤维化因子，研究表明，虽然TGF-β1和IGFBP-5都能激活间充质细胞以增加胶原蛋白和纤连蛋白的产生，但它们对上皮细胞的作用却截然不同。TGF-β1诱导上皮细胞死亡和/或上皮-间质转化（EMT），加剧组织结构的破坏。相比之下，IGFBP-5诱导上皮细胞在胶原蛋白或纤连蛋白基质上扩散，增加层粘连蛋白（上皮基底膜）的分泌，并在瘢痕组织中存在的营养匮乏条件下提高上皮细胞的存活率。因此，IGFBP-5可能会增强修复作用，可能是抗纤维化治疗的一个重要靶点。
