2. Academic Validation
  3. Gasdermin E deficiency attenuates acute kidney injury by inhibiting pyroptosis and inflammation

Gasdermin E deficiency attenuates acute kidney injury by inhibiting pyroptosis and inflammation

  • Cell Death Dis. 2021 Feb 1;12(2):139. doi: 10.1038/s41419-021-03431-2.
Weiwei Xia  # 1 2 3,  Yuanyuan Li  # 1 2 3,  Mengying Wu 1 2 3,  Qianqian Jin 1 2 3,  Qian Wang 1 2 3,  Shuzhen Li 1 2 3,  Songming Huang 1 2 3,  Aihua Zhang 1 2 3,  Yue Zhang 4 5 6,  Zhanjun Jia 7 8 9
Affiliations

Affiliations

  • 1 Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, 210008, Nanjing, China.
  • 2 Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, 210008, Nanjing, China.
  • 3 Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, 210029, Nanjing, China.
  • 4 Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, 210008, Nanjing, China. zyflora2006@hotmail.com.
  • 5 Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, 210008, Nanjing, China. zyflora2006@hotmail.com.
  • 6 Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, 210029, Nanjing, China. zyflora2006@hotmail.com.
  • 7 Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, 210008, Nanjing, China. jiazj72@hotmail.com.
  • 8 Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, 210008, Nanjing, China. jiazj72@hotmail.com.
  • 9 Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, 210029, Nanjing, China. jiazj72@hotmail.com.
  • # Contributed equally.
PMID: 33542198 DOI: 10.1038/s41419-021-03431-2
Abstract

Pyroptosis, one kind of inflammatory regulated cell death, is involved in various inflammatory diseases, including acute kidney injury (AKI). Besides Gasdermin D (GSDMD), GSDME is a newly identified mediator of Pyroptosis via the cleavage of Caspase-3 generating pyroptotic GSDME-N. Here, we investigated the role of GSDME in renal cellular Pyroptosis and AKI pathogenesis employing GSDME-deficient mice and human tubular epithelial cells (TECs) with the interventions of pharmacological and genetic approaches. After cisplatin treatment, GSDME-mediated Pyroptosis was induced as shown by the characteristic pyroptotic morphology in TECs, upregulated GSDME-N expression and enhanced release of IL-1β and LDH, and decreased cell viability. Strikingly, silencing GSDME in mice attenuated acute kidney injury and inflammation. The pyroptotic role of GSDME was also verified in human TECs in vitro. Further investigation showed that inhibition of Caspase-3 blocked GSDME-N cleavage and attenuated cisplatin-induced Pyroptosis and kidney dysfunction. Moreover, deletion of GSDME also protected against kidney injury induced by ischemia-reperfusion. Taken together, the findings from current study demonstrated that Caspase-3/GSDME-triggered Pyroptosis and inflammation contributes to AKI, providing new insights into the understanding and treatment of this disease.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12466
    ≥98.0%, Caspase-3抑制剂
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