Abstract
Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.
Highlights
acute kidney injury (AKI) is a set of clinical syndromes characterized by the rapid deterioration of the glomerular filtration rate [1]
Rat models of complete and incomplete repair of I/R-induced AKI To investigate the mechanisms of the AKI–chronic kidney disease (CKD) transition and the possible function of Hippo signalling in renal regeneration after AKI, we mimicked the complete and incomplete repair of I/R-induced AKI
Hippo signalling participates in renal regeneration after AKI To investigate whether Hippo signalling functions in renal regeneration after AKI, we evaluated the expression of key Hippo pathway components through protein analysis of the inner cortex and the outer medulla
Summary
AKI (acute kidney injury) is a set of clinical syndromes characterized by the rapid deterioration of the glomerular filtration rate [1]. After AKI occurs, the kidney possesses profound regenerative potential. It can recover either completely or incompletely after undergoing regeneration and repair [2,3]. Studies have substantiated a direct role for the tubule epithelium in the pathogenesis of the AKI–CKD transition [5,6]. Despite these previous findings, regulatory signalling during the transition should be clarified further. Kidney repair and regeneration after AKI occurs through the phenotypic switch of surviving epithelial cells from a mature quiescent to a proliferative state [5,6].
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