AI Article Synopsis
- The NLRP3 inflammasome is important in liver diseases, but its specific function in liver regeneration is not well understood.
- In a study with mice undergoing partial hepatectomy, it was found that inhibiting or removing NLRP3 improved liver regeneration, while increasing its levels hindered recovery.
- The benefits of NLRP3 depletion are linked to the activation of certain macrophages, and using drugs to inhibit NLRP3 showed promise in improving liver regeneration, especially in mice on a high-fat diet.
Article Abstract
The NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in human acute and chronic liver diseases. However, the role and cell-specific contribution of NLRP3 in liver regeneration remains unclear. Here, we found that NLRP3 was highly activated during the early stage of liver regeneration via 70% partial hepatectomy (PHx) mice model and clinical data. Global NLRP3 depletion or pharmacologically blocking NLRP3 significantly enhanced liver regeneration, while NLRP3 overexpression impaired it after PHx. Furthermore, mice with myeloid-specific knockout of (), rather than hepatocyte-specific knockout (), showed improved liver regeneration compared to control (). Mechanistically, deficiency of promoted myeloid-epithelial-reproductive tyrosine kinase (MerTK)-mediated efferocytosis, thereby inducing macrophages toward a pro-reparative Ly6C phenotype. Notably, NLRP3 inhibition by MCC950 effectively reversed the impairment of liver regeneration after PHx in mice fed a high-fat diet. Our findings provide a potential therapeutic strategy for the prevention and treatment of post-hepatectomy liver failure.
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| http://dx.doi.org/10.1126/sciadv.adq5786 | DOI Listing |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11691640 | PMC |
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Article Synopsis
- The NLRP3 inflammasome is important in liver diseases, but its specific function in liver regeneration is not well understood.
- In a study with mice undergoing partial hepatectomy, it was found that inhibiting or removing NLRP3 improved liver regeneration, while increasing its levels hindered recovery.
- The benefits of NLRP3 depletion are linked to the activation of certain macrophages, and using drugs to inhibit NLRP3 showed promise in improving liver regeneration, especially in mice on a high-fat diet.
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