title: Autophagy activation reduces renal tubular injury induced by urinary proteins.
abstract: Autophagy is shown to be beneficial for renal tubular injury caused by nephrotoxic drugs. To investigate whether autophagy could protect renal tubular epithelial cells (TECs) from injury induced by urinary proteins, we studied the activity and action of autophagy in TECs after urinary protein overload in vivo and in vitro. We found that autophagic vacuoles increased in TECs from patients with minimal change nephrotic syndrome (MCNS) and rat models with severe proteinuria induced by cationic BSA. In HK-2 cells, exposure to urinary proteins extracted from patients with MCNS led to a significant increase in autophagosome and autolysosome formation and decrease in SQSTM1/p62 protein level. Urinary protein addition also induced lysosomal turnover of LC3-II and perinuclear clustering of lysosomes. These changes were mediated by a reactive oxygen species (ROS)-dependent mechanism. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the production of LCN2/NGAL and HAVCR1/KIM-1 and the level of apoptosis induced by urinary proteins. In contrast, blocking autophagy with chloroquine or BECN1 siRNAs exerted an opposite effect. Similar results were also observed in animal models with proteinuria after treatments with rapamycin and chloroquine. Taken together, our results indicated an increase in autophagic flux, which mounts an adaptive response in TECs after urinary protein overload.
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Wei Jing
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Mian-Na
authors.initials: MN
authors.lastname: Luo
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Tan
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Lei-zhao
authors.initials: LZ
authors.lastname: Huang
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Urology; University of Kansas Medical Center; Kansas City, KS USA.
authors.forename: Benyi
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Nephrology; Guangdong Medical College; Zhanjiang, China.
authors.forename: Hua-feng
authors.initials: HF
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D002738:Chloroquine / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000293:injuries / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D008869:Microtubule-Associated Proteins; D002738:Chloroquine; D020123:Sirolimus
keywords: apoptosis; autophagic activation; autophagic pathway; tubular epithelial cells; urinary proteins