IGF2BP3 regulates macrophage-induced inflammation and liver damage in acute-on-chronic liver failure via the RORα-NF-κB signaling axis.

Autor: Cheng K; Department of Transplantation, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, Changsha, Hunan 410013, China., Liu K; Department of Transplantation, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, Changsha, Hunan 410013, China., Liu S; Department of Transplantation, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, Changsha, Hunan 410013, China., Zhao Y; Department of Transplantation, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, Changsha, Hunan 410013, China., Wang Q; Department of Transplantation, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, Changsha, Hunan 410013, China. Electronic address: wqiang@csu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt A), pp. 113030. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1016/j.intimp.2024.113030
Abstrakt: Acute-on-chronic liver failure (ACLF) is a severe condition characterized by high mortality rates, and macrophage-mediated inflammation plays a critical role in its progression. Our previous research has indicated the involvement of the RNA-binding protein IGF2BP3 in the pathogenesis of ACLF. However, the underlying molecular mechanisms contributing to this damage require further elucidation. Initially, we observed heightened expression of pro-inflammatory cytokines and macrophage activation in both ACLF patients and a mouse model induced by D-GalN/LPS. Subsequent loss-of-function experiments targeting IGF2BP3 revealed that the knockdown of IGF2BP3 potentially confers hepatoprotection by mitigating macrophage-induced inflammation. Further investigation using RNA Immunoprecipitation (RIP) assays and dual luciferase reporter assays confirmed that RORα is a target protein of the RNA-binding protein IGF2BP3. Importantly, depletion of RORα was found to significantly increase liver damage and inflammation by modulating the NF-κB signaling pathway. In conclusion, our findings underscore the crucial role of IGF2BP3 in mediating liver damage induced by activated macrophages in ACLF, which is regulated by the RORα-NF-κB signaling pathway. These discoveries offer novel insights into the pathogenesis and potential therapeutic targets for ACLF.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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