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您的检索式：作者名="Steven DCrowley"
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| 1 | FIH-1-modulated HIF-1α C-TAD promotes acute kidney injury to chronic kidney disease progression via regulating KLF5 signaling显示文摘Incomplete recovery from episodes of acute kidney injury(AKI)can predispose patients to develop chronic kidney disease(CKD).Although hypoxia-inducible factor-1α(HIF-1α)is a master regulator of the response to hypoxia/ischemia,the role of HIF-1α in CKD progression following incomplete recovery from AKI is poorly understood.Here,we investigated this issue using moderate and severe ischemia/reperfusion injury(I/RI)mouse models.We found that the outcomes of AKI were highly associated with the time course of tubular HIF-1α expression.Sustained activation of HIF-1α,accompanied by the development of renal fibrotic lesions,was found in kidneys with severe AKI.The AKI to CKD progression was markedly ameliorated when PX-478(a specific HIF-1α inhibitor,5 mg·kg^(−1)·d^(−1),i.p.)was administered starting on day 5 after severe I/RI for 10 consecutive days.Furthermore,we demonstrated that HIF-1α C-terminal transcriptional activation domain(C-TAD)transcriptionally stimulated KLF5,which promoted progression of CKD following severe AKI.The effect of HIF-1α C-TAD activation on promoting AKI to CKD progression was also confirmed in in vivo and in vitro studies.Moreover,we revealed that activation of HIF-1αC-TAD resulted in the loss of FIH-1,which was the key factor governing HIF-1α-driven AKI to CKD progression.Overexpression of FIH-1 inhibited HIF-1α C-TAD and prevented AKI to CKD progression.Thus,FIH-1-modulated HIF-1α C-TAD activation was the key mechanism of AKI to CKD progression by transcriptionally regulating KLF5 pathway.Our results provide new insights into the role of HIF-1α in AKI to CKD progression and also the potential therapeutic strategy for the prevention of renal diseases progression. | Zuo-lin Li Bin Wang Lin-li Lv Tao-tao Tang Yi Wen Jing-yuan Cao Xiao-xiao Zhu Song-tao Feng Steven DCrowley Bi-cheng Liu | 2021 | Acta Pharmacologica Sinica2021，42，12： | 3 |
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