{"doi":"10.1016/j.brci.2025.100013","title":"Resolution of inflammation increases erythropoiesis","abstract":"• 7,17-diHDPAn-3 exposure enhances erythropoiesis without affecting thrombocyte development. • 7,17-diHDPAn-3 action is mediated through inflammation resolution at a developmental time that supports hematopoietic stem cell formation. Erythropoiesis is a vital process for blood production, and its disruption contributes to various forms of anemia. In this study, we investigated the hematopoietic effects of bioactive lipid mediators derived from n-3 polyunsaturated fatty acids (n-3 PUFAs), focusing on a class of compounds known as specialized proresolving mediators (SPMs) that promote inflammation resolution. Using zebrafish embryos, we screened several n-3 PUFA–derived SPMs and identified 7(S),17(S)-dihydroxydocosapentaenoic acid (7,17-diHDPAn-3) that significantly enhances erythropoiesis. Exposure to 7,17-diHDPAn-3 upregulated gata1 , a key erythroid progenitor marker, and led to increased erythrocyte numbers in both primitive and definitive waves of erythropoiesis. Importantly, the production of platelets, which share a common progenitor with erythrocytes, was unaffected. Metabolomic analysis of sorted erythroid cells, using the transgenic zebrafish line Tg( gata1 :DsRed), revealed modest shifts in erythroid cell metabolic profiles. These findings suggest that the erythroid cells produced upon 7,17-diHDPAn-3 exposure, retain a metabolically acceptable profile. In parallel, RNA-sequencing analysis of these cells showed upregulation of hsp90 , a heat shock protein gene involved in heme biosynthesis, and downregulation of xpo1b , a gene associated with erythroid maturation. Although we also observed an increase in hematopoietic stem cell-associated genes such as cmyb and runx1 , these effects were relatively modest. In combination with dexamethasone, an anti-inflammatory steroid, 7,17-diHDPAn-3 further enhanced the expression of these gene markers, suggesting a potential link between inflammation resolution and early hematopoietic development. Our findings highlight 7,17-diHDPAn-3 as a promising candidate for promoting erythropoiesis and improving red blood cell recovery in vivo, with potential relevance to anemia treatment.","journal":"Blood Red Cells & Iron","year":2025,"id":571749,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"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":1115900,"name":"Carol K. Cox","orcid":null,"position":1,"is_corresponding":false},{"id":489004,"name":"Daniel Stephenson","orcid":"0000-0002-5698-3400","position":2,"is_corresponding":false},{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":3,"is_corresponding":false},{"id":1478105,"name":"Luciano Mendoza","orcid":null,"position":4,"is_corresponding":false},{"id":362387,"name":"Erin B. Taylor","orcid":"0000-0003-0122-0833","position":5,"is_corresponding":false},{"id":421036,"name":"Jerry D. Monroe","orcid":null,"position":6,"is_corresponding":false},{"id":351833,"name":"Yann Gibert","orcid":"0000-0001-8208-7223","position":7,"is_corresponding":false},{"id":1478104,"name":"Kim Uyen Cong Nguyen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:57:19.669553Z","pmid":"42389190","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":[]}