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Signal regulatory protein α protects podocytes through promotion of autophagic activity
Limin Li, … , Zhihong Liu, Ke Zen
Limin Li, … , Zhihong Liu, Ke Zen
Published May 2, 2019; First published March 19, 2019
Citation Information: JCI Insight. 2019;4(9):e124747. https://doi.org/10.1172/jci.insight.124747.
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Categories: Research Article Nephrology

Signal regulatory protein α protects podocytes through promotion of autophagic activity

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Abstract

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.

Authors

Limin Li, Ying Liu, Shan Li, Rong Yang, Caihong Zeng, Weiwei Rong, Hongwei Liang, Mingchao Zhang, Xiaodong Zhu, Koby Kidder, Yuan Liu, Zhihong Liu, Ke Zen

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Figure 3

SIRPα is specifically expressed on podocytes.

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SIRPα is specifically expressed on podocytes.
(A) SIRPα colocalizes with...
(A) SIRPα colocalizes with nephrin in mouse glomerulus. (B) SIRPα colocalizes with nephrin in human glomerulus. (C) SIRPα is expressed in mouse glomerular lysates but not tubular lysates (left) and in human podocytes (monocyte served as a positive control) but not human HK2 cells, endothelial cells, or mesangial cells (right). (D) Induction of SIRPα in differentiated mouse podocytes (MPC) (left) and human podocytes (HPC) (right). Scale bars: 25 μm.
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