Harris R C
Vanderbilt University School of Medicine, Nashville, TN, USA.
Adv Ren Replace Ther. 1997 Apr;4(2 Suppl 1):43-53.
The mammalian kidney is susceptible to injury by ischemia/reperfusion and toxins, and regeneration after injury is characterized by hyperplasia and recovery of the damaged epithelial cells that line the tubules. Locally produced growth factors may serve as mediators of nephrogenesis and differentiation during renal development and of renal regeneration after acute injury. In cultured cells, administration of one or a mixture of growth factors to quiescent cells will initiate progression through the cell cycle and cell division. In the adult kidney, cell division normally is very low, but will increase up to 10-fold after acute injury. In addition to proliferation after lethal injury, there also is cellular repair in cells that have undergone sublethal injury. Recent studies indicate that growth factors inhibit programmed cell death in response to acute injury. Growth factors also may initiate or promote protein and lipid biosynthesis and provide an intracellular milieu that promotes cellular repair. In addition to cellular repair, growth factors also may be involved in the re-establishment of cell-extracellular matrix and cell-cell integrity. Finally, growth factors may limit injury by decreasing the factors that induce damage. Increased local renal expression of growth factors in response to acute injury include heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I), transforming growth factor-beta, parathyroid hormone-related peptide, and acidic fibroblast growth factor. In a number of experimental models of acute renal injury, administration of exogenous growth factors has been shown to accelerate both structural and functional recovery. Specifically, EGF, IGF-1, and HGF all have been shown to be effective in this regard. These studies are reviewed and potential therapeutic uses of growth factors and cytokines will be discussed.
哺乳动物的肾脏易受缺血/再灌注和毒素的损伤，损伤后的再生表现为肾小管内衬受损上皮细胞的增生和恢复。局部产生的生长因子可能是肾脏发育过程中肾发生和分化以及急性损伤后肾脏再生的介质。在培养细胞中，向静止细胞施用一种或多种生长因子混合物会启动细胞周期进程和细胞分裂。在成年肾脏中，细胞分裂通常非常低，但急性损伤后会增加至10倍。除了致命损伤后的增殖外，经历亚致死损伤的细胞也存在细胞修复。最近的研究表明，生长因子可抑制急性损伤后的程序性细胞死亡。生长因子还可能启动或促进蛋白质和脂质生物合成，并提供促进细胞修复的细胞内环境。除了细胞修复外，生长因子还可能参与细胞-细胞外基质和细胞-细胞完整性的重建。最后，生长因子可能通过减少诱导损伤的因素来限制损伤。急性损伤后肾脏局部生长因子表达增加包括肝素结合表皮生长因子（HB-EGF）、肝细胞生长因子（HGF）、胰岛素样生长因子-I（IGF-I）、转化生长因子-β、甲状旁腺激素相关肽和酸性成纤维细胞生长因子。在许多急性肾损伤实验模型中，已证明施用外源性生长因子可加速结构和功能恢复。具体而言，EGF、IGF-1和HGF在这方面均已证明有效。本文将对这些研究进行综述，并讨论生长因子和细胞因子的潜在治疗用途。
