2. Academic Validation
  3. RacGAP1 ameliorates acute kidney injury by promoting proliferation and suppressing apoptosis of renal tubular cells

RacGAP1 ameliorates acute kidney injury by promoting proliferation and suppressing apoptosis of renal tubular cells

  • Biochem Biophys Res Commun. 2020 Jun 30;527(3):624-630. doi: 10.1016/j.bbrc.2020.04.140.
Weiran Zhou 1,  Shuan Zhao 2,  Sujuan Xu 1,  Zhaoxing Sun 1,  Yiran Liang 1,  Xiaoqiang Ding 3
Affiliations

Affiliations

  • 1 Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Medical Center of Kidney Disease, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Hemodialysis Quality Control Center of Shanghai, Shanghai, China.
  • 3 Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Medical Center of Kidney Disease, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Hemodialysis Quality Control Center of Shanghai, Shanghai, China. Electronic address: [email protected].
PMID: 32423815 DOI: 10.1016/j.bbrc.2020.04.140
Abstract

Background: Acute kidney injury (AKI) remains correlated with high mortality. Novel therapeutic strategies are urgently needed for AKI patients. Rac GTPase-activating protein 1 (RacGAP1) regulates the activity of RhoGTPase and acts as a predictive biomarker in several types of malignant tumor but the role of RacGAP1 in AKI has not been revealed.

Methods: Animal models of AKI induced by renal ischemia-reperfusion (I/R) and cisplatin treatment were generated in C57BL/6 mice. Hypoxia/reoxygenation (H/R) and cisplatin treatment were practiced in human renal tubular epithelial (HK-2) and renal tubular duct epithelial cells of rat (NRK-52E) cells. The role of RacGAP1 in cell proliferation and Apoptosis was estimated using western bolting, immunocytochemistry and flow cytometry. Verteporfin was used to activate the Hippo pathway to show whether the protective effects of RacGAP1 on cell growth and survival in renal tubular cells were dependent on the activation of YAP.

Results: The expression of RacGAP1 was significantly increased in mice kidneys after I/R or cisplatin treatment, combined with increased expression of RacGAP1 in H/R or cisplatin challenged cells. Overexpression of RacGAP1 protected HK2 and NRK-52E cells by promoting proliferation and decreasing Apoptosis. We also disclosed that RacGAP1 exerted its function through activation of YAP.

Conclusion: The present study provides evidence that RacGAP1 is involved in AKI. It promotes proliferation and limits Apoptosis of tubular epithelial cells via stimulating activation and nuclear translocation of YAP. Consequently, RacGAP1 may be a novel therapeutic target for AKI.

Keywords

AKI; Apoptosis; Proliferation; RacGAP1; YAP.

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