Chronic Cyclosporine Nephropathy Is Characterized by Excessive Autophagosome Formation and Decreased Autophagic Clearance

Abstract

Chronic CsA nephropathy is a state of excessive autophagic vacuoles and decreased autophagic clearance. Oxidative stress may play an importation role in the induction of autophagy.

TMBIM6 (transmembrane BAX inhibitor motif containing 6) enhances autophagy and reduces renal dysfunction in a cyclosporine A-induced nephrotoxicity model

“…19 In this study, we examined the effect of TMBIM6, a recently established regulator of ER stress and autophagy, on CsA-treated renal proximal tubule cells (HK-2 cells). First, we confirmed TMBIM6 mRNA expression with or without CsA-treated proximal tubule cells.…”

“…[52][53][54][55] Significant alterations of autophagy 19,56 have been reported in CsA-associated nephrotoxicity. CsA-induced renal injury is frequently observed in renal tubular structure including proximal tubules.…”

“…6A-C), indicating that stress may induce SQSTM1 accumulation in mouse tissues. 19,29 To visualize the ultrastructure of autophagy organelles in CsA-treated mice, we examined tissue specimens by transmission electron microscopy (Fig. 6D).…”

“…The dosage and route of administration for CsA were selected based on previous studies in mice. 19,68 Animals were anesthetized with ketamine one d after the treatment period was concluded, and blood and kidney tissue samples were collected.…”

“…17,18 Lysosome activity and the fusion process contribute to the maintenance and enhancement of autophagy. Chronic CsA nephropathy also causes excessive autophagosome formation and decreases autophagic clearance by disturbing the autophagy process, 19 suggesting that modulation of the autophagy process may counter CsA-induced nephrotoxicity.…”