Mizuno Shinya, Matsumoto Kunio, Nakamura Toshikazu
Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Front Biosci. 2008 May 1;13:7072-86. doi: 10.2741/3211.
Hepatocyte growth factor (HGF) and Met/HGF receptor play roles in dynamic growth and morphogenesis during development and regeneration of organs, including the kidney. In the kidney, HGF targets different types of cells, while its biological actions depend on a target cell type. During the earlier stages of chronic renal failure, renal HGF expression increased, but in later stages HGF expression decreased, associated with manifestation of chronic renal failure. When anti-HGF IgG was administered into mice with chronic renal failure, renal dysfunction and fibrosis were accelerated, indicating a role of endogenous HGF to suppress chronic renal failure. For myofibroblasts, a key cell type in tissue fibrosis, HGF exerted biological activities, including (i) inhibition of growth, (ii) suppression of fibrogenic cytokine expression, and (iii) enhancement of matrix metalloproteinases involved in subsequent apoptosis. In models of glomerular and tubulo-interstitial fibrosis, administration of HGF or HGF gene therapy improved renal fibrosis and dysfunction. Since insufficient production of HGF is causative for renal fibrosis, supplementation with HGF represents a new approach to inhibit or improve chronic renal failure.
肝细胞生长因子（HGF）和Met/HGF受体在包括肾脏在内的器官发育和再生过程中的动态生长和形态发生中发挥作用。在肾脏中，HGF作用于不同类型的细胞，其生物学作用取决于靶细胞类型。在慢性肾衰竭的早期阶段，肾脏HGF表达增加，但在后期阶段HGF表达下降，这与慢性肾衰竭的表现相关。当将抗HGF IgG给予慢性肾衰竭小鼠时，肾功能障碍和纤维化加速，表明内源性HGF具有抑制慢性肾衰竭的作用。对于肌成纤维细胞（组织纤维化中的关键细胞类型），HGF发挥生物学活性，包括（i）抑制生长，（ii）抑制促纤维化细胞因子表达，以及（iii）增强参与后续凋亡的基质金属蛋白酶。在肾小球和肾小管间质纤维化模型中，给予HGF或进行HGF基因治疗可改善肾纤维化和功能障碍。由于HGF产生不足是肾纤维化的病因，补充HGF代表了一种抑制或改善慢性肾衰竭的新方法。
