cMet agonistic antibody attenuates apoptosis in ischaemia‐reperfusion–induced kidney injury
Open Access
- 2 April 2020
- journal article
- research article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 24 (10), 5640-5651
- https://doi.org/10.1111/jcmm.15225
Abstract
Acute kidney injury (AKI) is a very common complication with high morbidity and mortality rates and no fundamental treatment. In this study, we investigated whether the hepatocyte growth factor (HGF)/cMet pathway is associated with the development of AKI and how the administration of a cMet agonistic antibody (Ab) affects an AKI model. In the analysis using human blood samples, cMet and HGF levels were found to be significantly increased in the AKI group, regardless of underlying renal function. The administration of a cMet agonistic Ab improved the functional and histological changes after bilateral ischaemia‐reperfusion injury. TUNEL‐positive cells and Bax/Bcl‐2 ratio were also reduced by cMet agonistic Ab treatment. In addition, cMet agonistic Ab treatment significantly increased the levels of PI3K, Akt and mTOR. Furthermore, after 24 hours of hypoxia induction in human proximal tubular epithelial cells, treatment with the cMet agonistic Ab also showed dose‐dependent antiapoptotic effects similar to those of the recombinant HGF treatment. Even when the HGF axis was blocked with a HGF‐blocking Ab, the cMet agonistic Ab showed an independent dose‐dependent antiapoptotic effect. In conclusion, cMet expression is associated with the occurrence of AKI. cMet agonistic Ab treatment attenuates the severity of AKI through the PI3K/Akt/mTOR pathway and improves apoptosis. cMet agonistic Ab may have important significance for the treatment of AKI.Keywords
Funding Information
- clinical research grant-in-aid from the Seoul National University Boramae Medical Center (03-2018-27)
- Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI17C1693)
This publication has 29 references indexed in Scilit:
- Activation of hepatocyte growth factor receptor, c-met, in renal tubules is required for renoprotection after acute kidney injuryKidney International, 2013
- Soluble c‐Met protein as a susceptible biomarker for gastric cancer risk: A nested case‐control study within the Korean Multicenter Cancer CohortInternational Journal of Cancer, 2012
- Soluble Epoxide Hydrolase Activity Determines the Severity of Ischemia-Reperfusion Injury in KidneyPLOS ONE, 2012
- Sulfatide-Reactive Natural Killer T Cells Abrogate Ischemia-Reperfusion InjuryJournal of the American Society of Nephrology, 2011
- Urine Analysis and Protein Networking Identify Met as a Marker of Metastatic Prostate CancerClinical Cancer Research, 2009
- Cell Confluence Regulates Hepatocyte Growth Factor-Stimulated Cell Morphogenesis in a β-Catenin-Dependent MannerMolecular and Cellular Biology, 2006
- Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized PatientsJournal of the American Society of Nephrology, 2005
- A Novel Mechanism by which Hepatocyte Growth Factor Blocks Tubular Epithelial to Mesenchymal TransitionJournal of the American Society of Nephrology, 2005
- Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of actionAmerican Journal of Physiology-Renal Physiology, 2004
- Ameliorative Effect of Hepatocyte Growth Factor on Glycerol-Induced Acute Renal Failure with Acute Tubular NecrosisNephron, 2002