Autophagy Dynamics and Modulation in a Rat Model of Renal Ischemia-Reperfusion Injury

International Journal of Molecular Sciences

Wim Martinet¹  Jean-Paul Decuypere²  Shawn Hutchinson²  Ina Jochmans²  Diethard Monbaliu²  Jacques Pirenne² 

[1] Department of Pharmaceutical Sciences, University of Antwerp, B-2610 Antwerp, Belgium;Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology and Immunology, KU Leuven, B-3000 Leuven, Belgium;

关键词: ischemia-reperfusion injury;    acute kidney injury;    autophagy;    apoptosis;    trehalose;   

DOI  :  10.3390/ijms21197185

来源: DOAJ

【 摘 要 】

Renal ischemia-reperfusion (IR) injury leading to cell death is a major cause of acute kidney injury, contributing to morbidity and mortality. Autophagy counteracts cell death by removing damaged macromolecules and organelles, making it an interesting anchor point for treatment strategies. However, autophagy is also suggested to enhance cell death when the ischemic burden is too strong. To investigate whether the role of autophagy depends on the severity of ischemic stress, we analyzed the dynamics of autophagy and apoptosis in an IR rat model with mild (45 min) or severe (60 min) renal ischemia. Following mild IR, renal injury was associated with reduced autophagy, enhanced mammalian target of rapamycin (mTOR) activity, and apoptosis. Severe IR, on the other hand, was associated with a higher autophagic activity, independent of mTOR, and without affecting apoptosis. Autophagy stimulation by trehalose injected 24 and 48 h prior to onset of severe ischemia did not reduce renal injury markers nor function, but reduced apoptosis and restored tubular dilation 7 days post reperfusion. This suggests that trehalose-dependent autophagy stimulation enhances tissue repair following an IR injury. Our data show that autophagy dynamics are strongly dependent on the severity of IR and that trehalose shows the potential to trigger autophagy-dependent repair processes following renal IR injury.

【 授权许可】

Unknown