Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia-reperfusion injury
Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia-reperfusion injury
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DOI：
10.4161/auto.19419
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发表时间：
2012-05-01
期刊：
影响因子：
13.3
通讯作者：
Huber, Tobias B.
中科院分区：
文献类型：
--
作者：
Liu, Shuya;Hartleben, Bjoern;Huber, Tobias B.
自噬负责蛋白质聚集体和受损细胞器的降解。一些研究报道了肾损伤后小管细胞的自噬活性增加。在这里，我们使用两种不同的小管特异性atg5敲除小鼠模型，研究了生理条件和应激条件下小管细胞自噬在体内的作用。虽然远端小管细胞中Atg5的缺失不会导致肾功能的显著改变，但远端和近端小管细胞中Atg5的缺失会导致肾功能受损。在生理条件下，atg5缺失的小管细胞显示出p62和氧化应激标志物的显著积累。引人注目的是，小管细胞atg5缺乏显著使肾脏对缺血性损伤敏感，导致肾功能受损，受损线粒体积聚以及小管细胞凋亡和增殖增加，突出了自噬在应激条件下维持小管细胞完整性的关键作用。
Autophagy is responsible for the degradation of protein aggregates and damaged organelles. Several studies have reported increased autophagic activity in tubular cells after kidney injury. Here, we examine the role of tubular cell autophagy in vivo under both physiological conditions and stress using two different tubular-specific Atg5-knockout mouse models. While Atg5 deletion in distal tubule cells does not cause a significant alteration in kidney function, deleting Atg5 in both distal and proximal tubule cells results in impaired kidney function. Already under physiological conditions, Atg5-null tubule cells display a significant accumulation of p62 and oxidative stress markers. Strikingly, tubular cell Atg5-deficiency dramatically sensitizes the kidneys to ischemic injury, resulting in impaired kidney function, accumulation of damaged mitochondria as well as increased tubular cell apoptosis and proliferation, highlighting the critical role that autophagy plays in maintaining tubular cell integrity during stress conditions.