Leucine‐rich repeat kinase 2 (LRRK2) is a known regulator of autophagy in a range of cell types. Here, we investigated the role of LRRK2‐associated autophagy during acute kidney injury (AKI) and its underlying mechanism(s) of action. Male mice aged 8‐weeks were treated with the LRRK2 inhibitor MLi‐2 and exposed to lipopolysaccharide (LPS) through intraperitoneal injection or ischemia–reperfusion (IR) surgery. Mice were sacrificed 12 or 24 h post‐LPS injection or IR operation and blood was collected for serum creatinine measurements. Kidney cortical tissues were collected for western blot analysis of podocyte‐specific markers and autophagy‐associated proteins. Renal histopathology was observed through hematoxylin‐eosin staining. For cell‐based assays, immortalized mouse podocytes were silenced for LRRK2 through siRNA transfection and exposed to LPS or cobalt chloride. Changes in cell viability were investigated using cell counting kit‐8, flow cytometry and MTT assays. Expression of podocyte‐specific markers and autophagy‐associated proteins were analyzed by western blotting. We observed an increase in LRRK2 expression at 12 h post‐LPS injection and IR surgery that was accompanied by enhanced autophagy. At 24 h post‐treatment, both LRRK2 expression and autophagy declined. Kidney injury was most pronounced in mice treated with MLi‐2. Podocytes silenced for LRRK2 showed a loss of cell viability, decreased levels of podocyte‐specific protein expression and a suppression of autophagy. Together, these data reveal the protective effects of LRRK2 during AKI through enhanced podocyte autophagy and cell viability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.