{"doi":"10.1126/scitranslmed.ade3157","title":"Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis","abstract":"Obesity is increasing worldwide and leads to a multitude of metabolic diseases, including cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis (NASH). Cysteine-rich angiogenic inducer 61 (CYR61) is associated with the progression of NASH, but it has been described to have anti- and proinflammatory properties. We sought to examine the role of liver CYR61 in NASH progression. CYR61 liver-specific knockout mice on a NASH diet showed improved glucose tolerance, decreased liver inflammation, and reduced fibrosis. CYR61 polarized infiltrating monocytes promoting a proinflammatory/profibrotic phenotype through an IRAK4/SYK/NF-κB signaling cascade. In vitro, CYR61 activated a profibrotic program, including PDGFa/PDGFb expression in macrophages, in an IRAK4/SYK/NF-κB-dependent manner. Furthermore, targeted-antibody blockade reduced CYR61-driven signaling in macrophages in vitro and in vivo, reducing fibrotic development. This study demonstrates that CYR61 is a key driver of liver inflammation and fibrosis in NASH.","journal":"Science Translational Medicine","year":2023,"id":326680,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1046217,"name":"Grace A. Yeung","orcid":"0009-0001-6484-3766","position":1,"is_corresponding":false},{"id":240356,"name":"Panu K. Luukkonen","orcid":"0000-0003-2085-679X","position":2,"is_corresponding":false},{"id":279404,"name":"Silvia Liu","orcid":"0000-0002-1840-9520","position":3,"is_corresponding":false},{"id":1046831,"name":"Muhammad Waqas Akbar","orcid":null,"position":4,"is_corresponding":false},{"id":273263,"name":"Gary J. Zhang","orcid":null,"position":5,"is_corresponding":false},{"id":1046218,"name":"Oluwashanu Balogun","orcid":"0000-0002-7474-5131","position":6,"is_corresponding":false},{"id":1046219,"name":"Xuemei Yu","orcid":"0000-0002-6494-3759","position":7,"is_corresponding":false},{"id":1046220,"name":"Rigen Mo","orcid":"0000-0003-4457-5052","position":8,"is_corresponding":false},{"id":369010,"name":"Kari Nejak‐Bowen","orcid":"0000-0001-6051-5338","position":9,"is_corresponding":false},{"id":651808,"name":"Masha V. Poyurovsky","orcid":"0000-0002-3024-778X","position":10,"is_corresponding":false},{"id":374037,"name":"Carmen J. Booth","orcid":"0000-0002-2153-738X","position":11,"is_corresponding":false},{"id":231799,"name":"Liza Konnikova","orcid":"0000-0003-4804-5497","position":12,"is_corresponding":false},{"id":232241,"name":"Gerald I. Shulman","orcid":"0000-0003-1529-5668","position":13,"is_corresponding":false},{"id":271168,"name":"Dean Yimlamai","orcid":"0000-0002-7936-7168","position":14,"is_corresponding":false},{"id":271156,"name":"Meghan Mooring","orcid":"0000-0002-8513-7430","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:08:37.840107Z","pmid":"37756381","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":[]}