TFEB
化学
尼福林
狭缝隔膜
基因敲除
信号转导
作者
Limin Liu,Ying Liu,Shan Li,Rong Yang,Caihong Zeng,Weiwei Rong,Hongwei Liang,Mingchao Zhang,Xiaodong Zhu,Koby Kidder,Yuan Liu,Zhihong Liu,Ke Zen
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2019-05-02
卷期号:4 (9)
被引量:12
标识
DOI:10.1172/jci.insight.124747
摘要
High autophagic activity in podocytes, terminally differentiated cells that serve as main components of the kidney filtration barrier, is essential for podocyte survival under various challenges. How podocytes maintain such a high level of autophagy, however, remains unclear. Here we report that signal regulatory protein α (SIRPα) plays a key role in promoting podocyte autophagy. Unlike other glomerular cells, podocytes strongly expressed SIRPα, which was, however, downregulated in patients with focal segmental glomerulosclerosis and mice with experimental nephropathy. Podocyte SIRPα levels were inversely correlated with the severity of podocyte injury and proteinuria but positively with autophagy. Compared with WT littermates, Sirpa-deficient mice displayed greater age-related podocyte injury and proteinuria and developed more rapid and severe renal injury in various models of experimental nephropathy. Mechanistically, podocyte SIRPα strongly reduced Akt/GSK-3β/β-catenin signaling, leading to an increase in autophagic activity. Our findings thus demonstrate a critical protective role of SIRPα in podocyte survival via maintenance of autophagic activity.
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