scholarly journals Loss of receptor interacting protein kinases 3 and caspase‐8 augments intrinsic apoptosis in tubular epithelial cell and promote kidney ischaemia‐reperfusion injury

Nephrology ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 661-669 ◽  
Author(s):  
Baekjun Sung ◽  
Ye Su ◽  
Jifu Jiang ◽  
Patrick Mcleod ◽  
Weihua Liu ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Reperfusion Injury ◽  
Protein Kinases ◽  
Tubular Epithelial Cell ◽  
Caspase 8 ◽  
Intrinsic Apoptosis ◽  
Ischaemia Reperfusion Injury ◽  
Interacting Protein ◽  
Ischaemia Reperfusion

scholarly journals Overexpression of A kinase interacting protein 1 attenuates myocardial ischaemia/reperfusion injury but does not influence heart failure development

2016 ◽  
Vol 111 (3) ◽  
pp. 217-226 ◽  
Author(s):  
Harmen G. Booij ◽  
Hongjuan Yu ◽  
Rudolf A. De Boer ◽  
Cees W.A. van de Kolk ◽  
Bart van de Sluis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Reperfusion Injury ◽  
Myocardial Ischaemia ◽  
Ischaemia Reperfusion Injury ◽  
Interacting Protein ◽  
Ischaemia Reperfusion

scholarly journals Mammalian STE20-Like Kinase 1 Deletion Alleviates Renal Ischaemia-Reperfusion Injury via Modulating Mitophagy and the AMPK-YAP Signalling Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2359-2376 ◽  
Author(s):  
Junxia Feng ◽  
Hongyan Li ◽  
Yunfang Zhang ◽  
Qi Wang ◽  
Shili Zhao ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Apoptosis ◽  
Tubular Epithelial Cell ◽  
Signalling Pathway ◽  
Ischaemia Reperfusion Injury ◽  
Renal Ischaemia ◽  
Ischaemia Reperfusion ◽  
Epithelial Cell Apoptosis

Background/Aims: The aim of our study is to investigate the molecular mechanism by which mammalian STE20-like kinase 1 (Mst1) participates in renal I/R injury through modifying mitophagy and the AMPK-YAP signalling pathway. Methods: WT mice and Mst1-knockout mice were subjected to renal ischaemia-reperfusion (I/R) in vivo. In vitro, the hypoxia-reoxygenation model was used with renal tubular epithelial cells to mimic renal I/R injury. Mitochondrial function was monitored via western blotting and immunofluorescence. Pathway blocker and siRNA knockout technology were used to establish the role of the AMPK-YAP signalling pathway in Mst1-mediated mitochondrial apoptosis in the setting of renal I/R injury. Results: Our data demonstrated that Mst1 expression was upregulated in response to renal I/R injury in vivo, and a higher Mst1 content was positively associated with renal dysfunction and more tubular epithelial cell apoptosis. However, genetic ablation of Mst1 improved renal function, alleviated reperfusion-mediated tubular epithelial cell apoptosis, and attenuated the vulnerability of kidney to I/R injury. In vitro, Mst1 upregulation induced mitochondrial damage including mitochondrial potential reduction, ROS overloading, cyt-c liberation and caspase-9 apoptotic pathway activation. At the molecular levels, I/R-mediated mitochondrial damage via repressing mitophagy and Mst1 suppressed mitophagy via inactivating AMPK signalling pathway and dowregulating OPA1 expression. Re-activation of AMPK-YAP-OPA1 signalling pathway provided a survival advantage for the tubular epithelial cell in the context of renal I/R injury by repressing mitochondrial fission. Conclusion: Overall, our results demonstrate that the pathogenesis of renal I/R injury is closely associated with an increase in Mst1 expression and the inactive AMPK-YAP-OPA1 signalling pathway. Based on this, strategies to repress Mst1 expression and activate mitophagy could serve as therapeutic targets to treat kidney ischaemia-reperfusion injury.

Sign in / Sign up

Export Citation Format

Share Document