Autophagy can repair endoplasmic reticulum stress damage of the passive Heymann nephritis model as revealed by proteomics analysis

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.

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► Label-free quantitative LC–MS was used for the first time to study PHN model.
► ERS‐related protein GRP78 and GRP94 were up-regulated in PHN.
► Cytoskeleton protein tubulin-β was down-regulated in PHN.
► ERS plays an important role in the podocyte damage.
► Autophagy can repair the cytoskeleton damage caused by ERS