Zang Xiujuan, Zheng Feng, Hong Hai-juan, Jiang Yan, Song Ying, Xia Yanping
Department of Nephrology, Songjiang Hospital Affiliated to the First People´s Hospital of Shanghai Jiaotong University, 746 Songjiang Zhongshan Road, Shanghai, 201600, China,
Int Urol Nephrol. 2014 Aug;46(8):1673-9. doi: 10.1007/s11255-014-0749-3. Epub 2014 Jun 28.
The aim of this study was to elucidate the role of neutrophil gelatinase-associated lipocalin (NGAL) in regulating apoptosis of tubular epithelial cells in a hypoxia-reperfusion model.
A hypoxia-reperfusion model was established with NRK-52E cells to assess apoptosis and cell cycle progression after the addition of NGAL. We investigated the expression of four apoptosis factors, Bcl-2, Bax, Fas and FasL, as well as the expression level of two NGAL receptors, 24p3R and megalin, by both Western blot and real-time PCR.
NGAL induced cell proliferation and reduced apoptosis by regulating four apoptosis factors Bcl-2, Bax, Fas and FasL. Western blot demonstrated that the two NGAL receptors, 24p3R and megalin, were increased after hypoxia-reperfusion, which was reduced by exogenous NGAL. Moreover, overexpression of the two receptors induced the expression of the anti-apoptotic factor Bcl-2 and reduced the expression of pro-apoptotic Bax, Fas and FasL.
These findings indicate that NGAL reduces apoptosis by regulating the four apoptosis factors Bcl-2, Bax, Fas and FasL through its two receptors 24p3R and megalin. These results also suggest that ectopic expression of NGAL in renal cells might provide a therapeutic strategy in ischemia-reperfusion by reducing apoptosis and promoting renal cell proliferation.
本研究旨在阐明中性粒细胞明胶酶相关脂质运载蛋白（NGAL）在缺氧再灌注模型中调节肾小管上皮细胞凋亡的作用。
用NRK - 52E细胞建立缺氧再灌注模型，以评估添加NGAL后的细胞凋亡和细胞周期进程。我们通过蛋白质免疫印迹法和实时聚合酶链反应研究了四种凋亡因子Bcl - 2、Bax、Fas和FasL的表达，以及两种NGAL受体24p3R和巨膜蛋白的表达水平。
NGAL通过调节四种凋亡因子Bcl - 2、Bax、Fas和FasL诱导细胞增殖并减少凋亡。蛋白质免疫印迹法表明，缺氧再灌注后两种NGAL受体24p3R和巨膜蛋白增加，而外源性NGAL可使其减少。此外，两种受体的过表达诱导了抗凋亡因子Bcl - 2的表达，并降低了促凋亡因子Bax、Fas和FasL的表达。
这些发现表明，NGAL通过其两种受体24p3R和巨膜蛋白调节四种凋亡因子Bcl - 2、Bax、Fas和FasL，从而减少细胞凋亡。这些结果还表明，在肾细胞中异位表达NGAL可能通过减少凋亡和促进肾细胞增殖为缺血再灌注提供一种治疗策略。
