Acute kidney injury(AKI) is a significant clinical complication with a substantial impact on morbidity and mortality, for which therapeutic options remain limited. The Hippo signaling pathway is an evolutionarily cons...Acute kidney injury(AKI) is a significant clinical complication with a substantial impact on morbidity and mortality, for which therapeutic options remain limited. The Hippo signaling pathway is an evolutionarily conserved pathway implicated in cell proliferation, dedifferentiation, and apoptosis via phosphorylation and inactivation of its downstream effectorsYes-associatedprotein(YAP)/transcriptional co-activator with PDZ-binding motif(TAZ). Recent studies have revealed that the Hippo pathway plays a pivotal role in the pathogenesis and repair of AKI. The Hippo pathway can mediate renal dysfunction through modulation of mitochondrial apoptosis under AKI conditions. Transient activation of YAP/TAZ in the acute phase of AKI may benefit renal recovery and regeneration, whereas persistent activation of YAP/TAZ in severe AKI may lead to maladaptive repair and transition to chronic kidney disease. This review aims to summarize recent findings on the associations between the Hippo pathway and AKI and to identify new therapeutic targets and strategies for AKI.展开更多
Acute kidney injury(AKI)is a major renal disease characterized by a sudden decrease in kidney function.After AKI,the kidney has the ability to repair,but if the initial injury is severe the repair may be incomplete or...Acute kidney injury(AKI)is a major renal disease characterized by a sudden decrease in kidney function.After AKI,the kidney has the ability to repair,but if the initial injury is severe the repair may be incomplete or maladaptive and result in chronic kidney problems.Autophagy is a highly conserved pathway to deliver intracellular contents to lysosomes for degradation.Autophagy plays an important role in maintaining renal function and is involved in the pathogenesis of renal diseases.Autophagy is activated in various forms of AKI and acts as a defense mechanism against kidney cell injury and death.After AKI,autophagy is maintained at a relatively high level in kidney tubule cells during maladaptive kidney repair but the role of autophagy in maladaptive kidney repair has been controversial.Nonetheless,recent studies have demonstrated that autophagy may contribute to maladaptive kidney repair after AKI by inducing tubular degeneration and promoting a profibrotic phenotype in renal tubule cells.In this review,we analyze the role and regulation of autophagy in kidney injury and repair and discuss the therapeutic strategies by targeting autophagy.展开更多
基金supported by the National Natural Science Foundation of China (82070718,81770712)Shanghai Science and Technology Innovation Natural Foundation(20ZR1444700)。
文摘Acute kidney injury(AKI) is a significant clinical complication with a substantial impact on morbidity and mortality, for which therapeutic options remain limited. The Hippo signaling pathway is an evolutionarily conserved pathway implicated in cell proliferation, dedifferentiation, and apoptosis via phosphorylation and inactivation of its downstream effectorsYes-associatedprotein(YAP)/transcriptional co-activator with PDZ-binding motif(TAZ). Recent studies have revealed that the Hippo pathway plays a pivotal role in the pathogenesis and repair of AKI. The Hippo pathway can mediate renal dysfunction through modulation of mitochondrial apoptosis under AKI conditions. Transient activation of YAP/TAZ in the acute phase of AKI may benefit renal recovery and regeneration, whereas persistent activation of YAP/TAZ in severe AKI may lead to maladaptive repair and transition to chronic kidney disease. This review aims to summarize recent findings on the associations between the Hippo pathway and AKI and to identify new therapeutic targets and strategies for AKI.
基金supported partly by grants from the National Natural Science Foundation of China(81720108008,82090024)the National Key R&D Program of China(2020YFC2005000).
文摘Acute kidney injury(AKI)is a major renal disease characterized by a sudden decrease in kidney function.After AKI,the kidney has the ability to repair,but if the initial injury is severe the repair may be incomplete or maladaptive and result in chronic kidney problems.Autophagy is a highly conserved pathway to deliver intracellular contents to lysosomes for degradation.Autophagy plays an important role in maintaining renal function and is involved in the pathogenesis of renal diseases.Autophagy is activated in various forms of AKI and acts as a defense mechanism against kidney cell injury and death.After AKI,autophagy is maintained at a relatively high level in kidney tubule cells during maladaptive kidney repair but the role of autophagy in maladaptive kidney repair has been controversial.Nonetheless,recent studies have demonstrated that autophagy may contribute to maladaptive kidney repair after AKI by inducing tubular degeneration and promoting a profibrotic phenotype in renal tubule cells.In this review,we analyze the role and regulation of autophagy in kidney injury and repair and discuss the therapeutic strategies by targeting autophagy.
