A comprehensive insight into autophagy and its potential signaling pathways as a therapeutic target in podocyte injury
Document Type
Article
Publication Date
2-1-2022
Abstract
As part of the glomerular filtration membrane, podocyte is terminally differentiated, structurally unique, and highly specialized in maintaining kidney function. Proteinuria caused by podocyte injury (foot process effacement) is the clinical symptom of various kidney diseases (CKD), including nephrotic syndrome. Podocyte autophagy has become a powerful therapeutic strategy target in ameliorating podocyte injury. Autophagy is known to be associated significantly with sirtuin-1, proteinuria, and podocyte injury. Various key findings in podocyte autophagy were reported in the past ten years, such as the role of endoplasmic reticulum (ER) stress in podocyte autophagy impairment, podocyte autophagy-related gene, essential roles of the signaling pathways: Mammalian Target of Rapamycin (mTOR)/ Phosphoinositide 3-kinase (PI3k)/ serine/threonine kinase 1 (Akt) in podocyte autophagy. These significant factors caused podocyte injury associated with autophagy impairment. Sirtuin-1 was reported to have a vital key role in mTOR signaling, 5 ` AMP-activated protein kinase (AMPK) regulation, autophagy activation, and various critical pathways associated with podocyte's function and health; it has potential value to podocyte injury pathogenesis investigation. From these findings, podocyte autophagy has become an attractive therapeutic strategy to ameliorate podocyte injury, and this review will provide an indepth review on therapeutic targets he podocyte autophagy.
Keywords
Podocyte injury, Podocyte autophagy, MTOR signaling pathway, Diabetic nephropathy, Glomerulopathy, Sirtuin-1
Divisions
fac_med
Funders
University of Malaya Medical Centre (UMMC) Clinical Investigation Centre (CIC) Clinical Trial Fund,Research University Grant Scheme by Universiti Teknologi Malaysia (UTM) : Tier 2 grant [Grant No: Q. J130000.2651.18J09],UTM Fundamental Research grant [Grant No: Q. J130000.2551.21H36]
Publication Title
International Journal of Biochemistry & Cell Biology
Volume
143
Publisher
Pergamon-Elsevier Science Ltd
Publisher Location
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND