title: Autophagy can repair endoplasmic reticulum stress damage of the passive Heymann nephritis model as revealed by proteomics analysis.
abstract: Membranous nephropathy is a common cause of nephrotic syndrome in adults. Although many mechanisms have been proposed, whole proteomic research is still lacking. We analyzed the passive Heymann nephritis animal model using label-free quantitative proteome technology. Results showed 160 differential proteins between control and PHN model groups at days 14 and 21. The expression level of endoplasmic reticulum stress (ERS)-associated protein GRP78 and GRP94 protein was up-regulated on day 14 or 21, which was confirmed by Western blotting. The results also showed that the autophagy marker LC3 was up-regulated in the models. Furthermore, we used tunicamycin to induce ERS of podocytes in vitro to investigate the mechanism. Results of Western blotting revealed that the expression of GRP78, GRP94, and LC3 was up-regulated, while that of the cytoskeletal protein tubulin-β was down-regulated, and immunofluorescence displayed disordered distribution of tubulin-β. These suggest that ERS plays an important role in podocyte damage. Autophagy can repair the cytoskeleton damage caused by ERS as a protective mechanism. This provides an important basis for a thorough understanding of the mechanism of podocyte damage and the pathogenesis of membranous nephropathy.
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Cui
authors.forename: Kai
authors.initials: K
authors.lastname: Hou
authors.forename: Huabin
authors.initials: H
authors.lastname: Su
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Huang
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D015433:Glomerulonephritis, Membranous / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D026541:Heymann Nephritis Antigenic Complex / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; C051684:GRP78 protein, rat; C000717248:Hspa5 protein, mouse; C526109:Anxa3 protein, rat; C053387:endoplasmin