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Gasdermin D–mediated pyroptosis suppresses liver regeneration after 70% partial hepatectomy
Pyroptosis is a kind of programmed cell death primarily mediated by gasdermin D (GSDMD) and shown to regulate multiple diseases. However, its contribution to liver regeneration, a fine‐tuned tissue repair process mediated primarily by hepatocytes after mass loss, remains unclear. Herein, we found th...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426395/ https://www.ncbi.nlm.nih.gov/pubmed/35509206 http://dx.doi.org/10.1002/hep4.1973 |
Sumario: | Pyroptosis is a kind of programmed cell death primarily mediated by gasdermin D (GSDMD) and shown to regulate multiple diseases. However, its contribution to liver regeneration, a fine‐tuned tissue repair process mediated primarily by hepatocytes after mass loss, remains unclear. Herein, we found that caspase‐11/GSDMD‐mediated pyroptosis was activated in regenerating liver after 70% partial hepatectomy. Impeding pyroptosis by deleting GSDMD significantly reduced liver injury and accelerated liver regeneration. Mechanistically, GSDMD deficiency up‐regulates the activation of hepatocyte growth factor/c‐Met and epidermal growth factor receptor mitogenic pathways at the initiation phase. Moreover, activin A and glypican 3 (GPC3), two terminators of liver regeneration, were inhibited when GSDMD was absent. In vitro study suggested the expressions of activin A and GPC3 were induced by interleukin (IL)–1β and IL‐18, whose maturations were regulated by GSDMD‐mediated pyroptosis. Similarly, pharmacologically inhibiting GSDMD recapitulates these phenomena. Conclusion: This study characterizes the role of GSDMD‐mediated pyroptosis in liver regeneration and lays the foundation for enhancing liver restoration by targeting GSDMD in liver patients with impaired regenerative capacity. |
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