{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["88"],"submitter":["Yang S"],"pubmed_abstract":["Hepatic stellate cells (HSCs) trans-differentiation into myofibroblasts is central to liver fibrosis. Integrated stress response (ISR) signaling, including metabolic stress, plays a critical role in this process. However, the precise role of ISR signaling in HSCs activation-whether detrimental or protective-remains unclear. Here we identified that the noncanonical cap-binding protein EIF3d-mediated ATF4 expression is significantly upregulated in HSCs from both patients and mouse models of fibrotic livers, with its levels positively correlating with the degree of fibrosis. EIF3d-ATF4 signaling was induced by TGFβ1 in HSCs and was demonstrated to be both necessary and sufficient for promoting HSC survival, proliferation, activation, and extracellular matrix (ECM) production. Furthermore, gen"],"journal":["Redox biology"],"pagination":["103905"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12637262"],"repository":["biostudies-literature"],"pubmed_title":["Integrated stress response-mediated metabolic reprogramming drives hepatic stellate cell activation and liver fibrosis via the noncanonical EIF3d-ATF4-S100P signaling pathway."],"pmcid":["PMC12637262"],"pubmed_authors":["Liu X","Li Y","Chen Z","Zhang H","Nie Z","Zai W","Chen W","Sun X","Yang S","Kong Y","Wang Z","Gao S"],"additional_accession":[]},"is_claimable":false,"name":"Integrated stress response-mediated metabolic reprogramming drives hepatic stellate cell activation and liver fibrosis via the noncanonical EIF3d-ATF4-S100P signaling pathway.","description":"Hepatic stellate cells (HSCs) trans-differentiation into myofibroblasts is central to liver fibrosis. Integrated stress response (ISR) signaling, including metabolic stress, plays a critical role in this process. However, the precise role of ISR signaling in HSCs activation-whether detrimental or protective-remains unclear. Here we identified that the noncanonical cap-binding protein EIF3d-mediated ATF4 expression is significantly upregulated in HSCs from both patients and mouse models of fibrotic livers, with its levels positively correlating with the degree of fibrosis. EIF3d-ATF4 signaling was induced by TGFβ1 in HSCs and was demonstrated to be both necessary and sufficient for promoting HSC survival, proliferation, activation, and extracellular matrix (ECM) production. Furthermore, gen","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-05T19:46:29.086Z","creation":"2026-05-21T03:11:55.294Z"},"accession":"S-EPMC12637262","cross_references":{"pubmed":["41197183"],"doi":["10.1016/j.redox.2025.103905"]}}