{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hong R"],"funding":["shandong provincial natural science foundation","MOST | National Natural Science Foundation of China (NSFC)","MOST | National Natural Science Foundation of China"],"pagination":["1055-1074"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10933415"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(3)"],"pubmed_abstract":["Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-β (TGF-β), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-β-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis."],"journal":["EMBO reports"],"pubmed_title":["XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis."],"pmcid":["PMC10933415"],"funding_grant_id":["32000524","31991193","32100948","ZR2020QC076"],"pubmed_authors":["Yang J","Li D","Liu M","Ni H","Yu F","Sun T","Zhong W","Wang J","Yang Y","Huang Z","Bu W","Li T","Tian X","Tan Y","Wang X","Yang S","Hong R","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis.","description":"Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. However, the molecular basis for HSC activation remains poorly understood. Herein, we demonstrate that primary cilia are present on quiescent HSCs but exhibit a significant loss upon HSC activation which correlates with decreased levels of the ciliary protein intraflagellar transport 88 (IFT88). Ift88-knockout mice are more susceptible to chronic carbon tetrachloride-induced liver fibrosis. Mechanistic studies show that the X-linked inhibitor of apoptosis (XIAP) functions as an E3 ubiquitin ligase for IFT88. Transforming growth factor-β (TGF-β), a profibrotic factor, enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-β-induced HSC activation and liver fibrosis. These findings reveal a previously unrecognized role for ciliary homeostasis in regulating HSC activation and identify the XIAP-IFT88 axis as a potential therapeutic target for liver fibrosis.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-26T14:17:13.103Z","creation":"2025-04-06T14:33:54.438Z"},"accession":"S-EPMC10933415","cross_references":{"pubmed":["38351372"],"doi":["10.1038/s44319-024-00092-y"]}}