ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2025
ATF6 Alleviates Endothelial Inflammation Following Extended Hepatectomy Through Inhibition of TRIM10/NF-κB Signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Ceapin-A7 counteracts the protective effects of Lanreotide in endothelial cells.Aspects of molecular medicine · 2026Article
- ATF6 Alleviates Endothelial Inflammation Following Extended Hepatectomy Through Inhibition of TRIM10/NF-κB Signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
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11 authors.
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Abstract
The inflammatory response in liver sinusoidal endothelial cells (LSECs) is crucial to the pathophysiology of postoperative hepatic failure. The unfolded protein response (UPR) in LSECs following surgical stress exerts an important mechanism for resolving endothelial inflammation and re-establishing liver homeostasis. We employed 80% hepatectomy in mice to simulate extended hepatectomy and verified the gene expression in the patients who underwent marginal hepatectomy. The UPR in LSECs and endothelial inflammation were induced with tunicamycin or lipopolysaccharides in HUVECs to investigate the expression, effect, and regulation of activating transcription factor 6 (ATF6) in endothelial inflammation. We found that UPR protein ATF6 in LSECs was upregulated and activated following extended hepatectomy in both mice and humans; ATF6 deficiency in mice by either global knockout or LSECs-specific knockdown failed to alleviate the inflammatory response and led to severe liver injury; genetic knockout or pharmacological inhibition of ATF6 by the ATF6 antagonist Ceapin-A7 in HUVECs led to severe inflammation through the nuclear factor-κB (NF-κB) signaling pathway, while the ATF6 agonist AA147 ameliorated inflammation. Mechanistically, ATF6 induced negative transcriptional control of tripartite motif-containing protein 10 (TRIM10) and the downstream NF-κB signaling pathway, thereby suppressing endothelial inflammation. Taken together, our data identify ATF6 as a suppressor of endothelial inflammation following extended hepatectomy and clarify the underlying regulatory mechanism of the ATF6-TRIM10/NF-κB signaling pathway. These findings highlight its potential as a therapeutic target for postoperative hepatic failure.
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