Man Yu-Lin, Rui Hong-Liang, Chen Yi-Pu, Wang Guo-Qin, Sun Li-Jun, Cheng Hong
Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Evid Based Complement Alternat Med. 2017;2017:9596256. doi: 10.1155/2017/9596256. Epub 2017 Oct 18.
Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial-to-myofibroblast transition (EMT). However, the relationship between AA-induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation. The enhancement of autophagy using autophagy inducers, rapamycin or serum-free medium, led to an aggravation of EMT and upregulated expression of fibronectin, a component of extracellular matrix, in AA-treated HKC cells. In contrast, the inhibition of autophagy by autophagy inhibitor, 3-methyladenine, or by knockdown of led to an attenuation of EMT and downregulated expression of fibronectin in AA-treated HKC cells. Taken together, our study suggests that, after AA stimulation, two types of cell responses of HKC cells, autophagy and EMT, will successively appear, and autophagy can promote EMT of HKC.
自噬在肾脏细胞内稳态中起着至关重要的作用。先前的研究发现，马兜铃酸（AA）可诱导肾小管上皮细胞自噬以及上皮-间充质转化（EMT）。然而，AA诱导的自噬与EMT之间的关系尚不清楚。我们的结果表明，在AA刺激后，自噬的出现先于EMT。HKC细胞的自噬从第3小时开始逐渐增加，在第12小时达到峰值，然后逐渐减弱直至第36小时；HKC的EMT过程在AA刺激后从第6小时到第36小时持续增加。使用自噬诱导剂雷帕霉素或无血清培养基增强自噬，导致AA处理的HKC细胞中EMT加重，细胞外基质成分纤连蛋白的表达上调。相反，使用自噬抑制剂3-甲基腺嘌呤或通过敲低抑制自噬，导致AA处理的HKC细胞中EMT减弱，纤连蛋白的表达下调。综上所述，我们的研究表明，在AA刺激后，HKC细胞的两种细胞反应，即自噬和EMT，将相继出现，并且自噬可促进HKC的EMT。
