Hepatocyte growth factor protects renal epithelial cells from apoptotic cell death.
Hepatocyte growth factor protects renal epithelial cells from apoptotic cell death.
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肝细胞生长因子可保护肾上皮细胞免于凋亡细胞死亡。
DOI：
10.1006/bbrc.1998.8676
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Dworkin,LD
中科院分区：
文献类型：
--
作者：
Liu,Y;Sun,AM;Dworkin,LD
肝细胞生长因子（HGF）是一种多效性因子，在损伤后的肾小管修复和再生中起重要作用。研究表明，给予动物外源性HGF可刺激肾上皮细胞DNA合成，加速急性肾功能衰竭（ARF）的恢复。然而，细胞增殖的增加是否是ARF中HGF的所有有益作用的原因尚不清楚。在这项研究中，我们证明，肝细胞生长因子保护肾上皮细胞发生凋亡细胞死亡。通过荧光染料H-33342染色、TUNEL染色、光学和电子显微镜以及DNA梯状分析评估，在无血清培养基中用25 μM顺铂处理肾上皮mIMCD-3细胞可诱导显著的凋亡。然而，通过转染在mIMCD-3细胞中组成型表达HGF导致对顺铂诱导的凋亡性死亡的抗性。用25 μM顺铂处理2天后，产生HGF的C1细胞的存活率比对照mIMCD-3细胞高2倍以上。这些结果表明，肝细胞生长因子不仅可以激活肾小管修复过程，而且还可以通过保护肾上皮细胞免于凋亡来改善初始损伤。
Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential role in renal tubular repair and regeneration following injury. Studies indicate that administration of exogenous HGF to animals stimulates renal epithelial cell DNA synthesis and accelerates recovery from acute renal failure (ARF). However, whether increased cell proliferation accounts for all of the beneficial effects of HGF in ARF is unknown. In this study, we demonstrate that HGF protects renal epithelial cells from undergoing apoptotic cell death. Treatment of renal epithelial mIMCD-3 cells with 25 μM cisplatin in the serum-free medium induced significant apoptosis, as assessed by fluorescent Dye H-33342 staining, TUNEL staining, light and electron microscopy, and DNA laddering analysis. However, constitutive expression of HGF by transfection in mIMCD-3 cells resulted in resistance to cisplatin-induced apoptotic death. The survival rate of HGF-producing C1 cells was more than 2-fold greater as compared to control, mIMCD-3 cells following treatment with 25 μM cisplatin for 2 days. These results suggest that HGF may not only activate tubular repair processes but also ameliorate the initial injury by protecting renal epithelial cells from undergoing apoptosis.