Signal regulatory protein ? protects podocytes through promoting autophagic activity.

ABSTRACT: High autophagic activity in podocytes, terminally differentiated cells which 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 ? (SIRP?) plays a key role in promoting podocyte autophagy. Unlike other glomerular cells, podocytes strongly express SIRP?, which is, however, downregulated in patients with focal segmental glomerulosclerosis and mice with experimental nephropathy. Podocyte SIRP? levels are inversely correlated with the severity of podocyte injury and proteinuria but positively with autophagy. Compared to wild-type littermates, Sirpa-deficient mice display greater age-related podocyte injury and proteinuria and develop more rapid and severe renal injury in various models of experimental nephropathy. Mechanistically, podocyte SIRP? strongly reduces Akt/GSK-3?/?-catenin signaling, leading to an increase in autophagic activity. Our findings thus demonstrate a critical protective role of SIRP? in podocyte survival via maintaining autophagic activity.

SUBMITTER: Li L 

PROVIDER: S-EPMC6538339 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature