USP11 promotes renal tubular cell pyroptosis and fibrosis in UUO mice via inhibiting KLF4 ubiquitin degradation.

The pyroptosis of renal tubular epithelial cells leads to tubular loss and inflammation and then promotes renal fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) can bidirectionally regulate the transcription of target genes. Our previous study revealed that sustained elevation of KLF4 is responsible for the transition of acute kidney injury (AKI) into chronic kidney disease (CKD) and renal fibrosis.

Deubiquitinating enzyme USP11 promotes renal tubular cell senescence and fibrosis via inhibiting the ubiquitin degradation of TGF-β receptor II.

Transforming growth factor-β1 (TGF-β1) is regarded as a key factor in promoting renal fibrosis during chronic kidney disease (CKD). Signaling transduction of TGF-β1 starts with binding to TGF-β type II receptor (Tgfbr2), a constitutively activated kinase that phosphorylates TGF-β type I receptor (Tgfbr1), and then activates downstream Smad2/3 or noncanonical pathways. Previous studies show that cellular senescence is associated with the progression of CKD, and accelerated tubular cell senescence is implicated in promoting renal fibrosis.

[Acute kidney injury and regulated cell death].

Acute kidney injury (AKI) refers to a clinical syndrome in which renal function declines rapidly in a short period of time caused by various pathological factors. During the development of AKI, renal tubules with the functions of reabsorption and excretion are prone to cell death due to external pathological stimuli, which is an important cause of impaired renal function. In recent years, a variety of new cell death pathways have been gradually recognized.

Caspase-11 promotes NLRP3 inflammasome activation via the cleavage of pannexin1 in acute kidney disease.

Ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) in clinic. The activation of NLRP3 inflammasome is associated with inflammation and renal injury in I/R-induced AKI. In the current study we explored the molecular and cellular mechanisms for NLRP3 inflammasome activation following renal I/R.

KLF4 initiates sustained YAP activation to promote renal fibrosis in mice after ischemia-reperfusion kidney injury.

Acute renal injury (AKI) causes a long-term risk for progressing into chronic kidney disease (CKD) and interstitial fibrosis. Yes-associated protein (YAP), a key transcriptional cofactor in Hippo signaling pathway, shuttles between the cytoplasm and nucleus, which is required for the renal tubular epithelial cells repair in the acute phase of AKI. In this study we investigated the role of YAP during ischemia-reperfusion (IR)-induced AKI to CKD.