{"doi":"10.1002/hep4.2057","title":"Cellular communication network factor 1‐stimulated liver macrophage efferocytosis drives hepatic stellate cell activation and liver fibrosis","abstract":"Abstract Following inflammatory injury in the liver, neutrophils quickly infiltrate the injured tissue to defend against microbes and initiate the repair process; these neutrophils are short lived and rapidly undergo apoptosis. Hepatic stellate cells (HSCs) are the principal precursor cells that transdifferentiate into myofibroblast‐like cells, which produce a large amount of extracellular matrix that promotes repair but can also lead to fibrosis if the injury becomes chronic. The matricellular protein cellular communication network factor 1 (CCN1) acts as a bridging molecule by binding phosphatidylserine in apoptotic cells and integrin α v β 3 in phagocytes, thereby triggering efferocytosis or phagocytic clearance of the apoptotic cells. Here, we show that CCN1 induces liver macrophage efferocytosis of apoptotic neutrophils in carbon tetrachloride (CCl 4 )‐induced liver injury, leading to the production of activated transforming growth factor (TGF)‐β1, which in turn induces HSC transdifferentiation into myofibroblast‐like cells that promote fibrosis development. Consequently, knock‐in mice expressing a single amino acid substitution in CCN1 rendering it unable to bind α v β 3 or induce efferocytosis are impaired in neutrophil clearance, production of activated TGF‐β1, and HSC transdifferentiation, resulting in greatly diminished liver fibrosis following exposure to CCl 4 . Conclusion: These results reveal the crucial role of CCN1 in stimulating liver macrophage clearance of apoptotic neutrophils, a process that drives HSC transdifferentiation into myofibroblastic cells and underlies fibrogenesis in chronic liver injury.","journal":"Hepatology Communications","year":2022,"id":253671,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":853825,"name":"Naiyuan Cheng","orcid":null,"position":1,"is_corresponding":false},{"id":233464,"name":"Lester F. Lau","orcid":"0000-0002-4364-2914","position":2,"is_corresponding":false},{"id":852922,"name":"KH Kim","orcid":"0000-0001-8265-6609","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T00:24:59.596040Z","pmid":"35929736","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}