title: Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector.
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.
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R. China.
authors.forename: Pei-Xue
authors.initials: PX
authors.lastname: Li
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, U.S.A.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R. China.
authors.forename: Meng-Xin
authors.initials: MX
authors.lastname: Yin
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Central Hospital of TaiAn, TaiAn, Shandong 271000, P.R. China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Sun
authors.affiliation: Division of Nephrology, No. 456 Hospital of PLA, Jinan, Shandong 250031, P.R. China.
authors.forename: Zeng-Bo
authors.initials: ZB
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Yueyang Hospital, Shanghai 200437, P.R. China.
authors.forename: Xiang-Chen
authors.initials: XC
authors.lastname: Gu
authors.affiliation: Laboratory of Angiogenesis and Neurovascular link, Vesalius Research Center, VIB, Leuven, B-3000, Belgium.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Fu
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Hu
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: He
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R. China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R. China.
authors.forename: Zhao-Liang
authors.initials: ZL
authors.lastname: Fei
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R. China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R. China chlmei1954@126.com rayzhang@sibcb.ac.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Kidney Institute of CPLA, Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, P.R. China chlmei1954@126.com rayzhang@sibcb.ac.cn.
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Mei
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D004074:Digitoxin / Q000494:pharmacology; D005260:Female; D005355:Fibrosis; D055785:Gene Knockdown Techniques / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects; D000091102:YAP-Signaling Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C509425:Yap1 protein, rat; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D004074:Digitoxin; C000591484:Lats1 protein, rat; D017346:Protein Serine-Threonine Kinases
keywords: Hippo pathway; Yes-associated protein (YAP); acute kidney injury; chronic kidney disease; fibrogenesis; repair