{"doi":"10.1016/j.jhepr.2025.101454","title":"Resolvin D1-mediated cellular crosstalk protects against MASH","abstract":"Background & aims: Recent studies have highlighted the beneficial effect of resolvin D1 (RvD1), a docosahexaenoic acid-derived specialized pro-resolving mediator, on chronic liver diseases, but the underlying mechanisms are not well understood. Our study aimed to determine the role and mechanism of RvD1-mediated cellular crosstalk in metabolic dysfunction-associated steatohepatitis (MASH). Methods: RvD1 was administered to mice with experimental MASH, followed by bulk and single cell RNA sequencing (scRNA-seq) analysis. Primary liver cells, including primary hepatocytes, Kupffer cells (KCs), T cells, and hepatic stellate cells (HSCs), were isolated for co-culture experiments to elucidate the effect of RvD1 on cell death, inflammation, and fibrosis. Results: <0.05). Mechanistically, RvD1 reduced hepatocyte death by suppressing endoplasmic reticulum (ER) stress. Co-culture experiments with primary liver cells showed that conditioned media from palmitic acid-treated hepatocytes activated KCs, T cells, and HSCs; however, those effects were abolished from RvD1-pretreated hepatocytes. Moreover, RvD1 directly suppressed T cell activation and IFNγ production, leading to reduced Stat1-Cxcl10 signaling in KCs. Conclusions: RvD1 reduced hepatocyte death and DAMP production by alleviating ER stress-mediated apoptosis, leading to decreased activation of KCs, T cells, and HSCs. This study highlights the novel role of RvD1-mediated cellular crosstalk among different liver cells in MASH. Impact and implications: MASH is a growing healthcare burden worldwide. However, current treatments for MASH and its sequelae remain limited. Recent studies highlighted the therapeutic benefit of specialized pro-resolving mediators (SPMs), including RvD1, in liver diseases. However, the mechanisms underlying these beneficial effects are not well understood. Based on a series of co-culture primary cell experiments and unbiased transcriptomic analyses, we show that RvD1-mediated cellular crosstalk among hepatocytes and nonparenchymal cells protects against MASH progression. Our study provides a new mechanistic insight into the role of RvD1 in MASH and highlights its therapeutic potential to treat this condition.","journal":"JHEP Reports","year":2025,"id":538233,"datarank":0.26089254978994,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.01947686292482491,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.01947686292482491,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9644,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1372311,"name":"Yiwei Zhu","orcid":"0000-0001-9789-7229","position":1,"is_corresponding":false},{"id":258780,"name":"Fanglin Ma","orcid":"0000-0002-7251-9544","position":2,"is_corresponding":false},{"id":416558,"name":"Neha Gupta","orcid":"0000-0001-8181-7378","position":3,"is_corresponding":false},{"id":1283515,"name":"Haley Asplund","orcid":null,"position":4,"is_corresponding":false},{"id":1233504,"name":"Bruno Cogliati","orcid":"0000-0002-1388-7240","position":5,"is_corresponding":false},{"id":391248,"name":"Jerry E. 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Sansbury","orcid":"0000-0002-6339-2940","position":9,"is_corresponding":false},{"id":629785,"name":"Xin Huang","orcid":"0000-0002-6208-4751","position":10,"is_corresponding":false},{"id":246025,"name":"Bishuang Cai","orcid":"0000-0002-2047-9923","position":11,"is_corresponding":false},{"id":298732,"name":"Amaia Navarro‐Corcuera","orcid":"0000-0001-6026-8285","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:21.389196Z","pmid":"40671835","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":[]}