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Neuregulin\u20101 (NRG\u20101) is a cytoprotective growth factor with anti\u2010inflammatory and antioxidant properties and an established clinical safety profile in humans. Using Townes humanized sickle cell (HbSS) mice, we investigated whether NRG\u20101 mitigates kidney injury by reducing hemolytic and inflammatory mediators and enhancing renal cytoprotective and repair factors. NRG\u20101 treatment reduced plasma heme, lactate dehydrogenase, and pro\u2010inflammatory cytokines levels, while increasing the proportion of circulating fetal hemoglobin\u2010containing red blood cells (F\u2010cells). Treatment mitigated urinary cystatin C and neutrophil gelatinase\u2010associated lipocalin (NGAL)\u00a0elevations and improved renal histopathology, including reduced iron deposition, glomerular congestion, and sclerosis. NRG\u20101 also enhanced heme oxygenase\u20101 (HO\u20101) expression in HbSS kidneys and increased urinary renal repair biomarkers clusterin and epidermal growth factor (EGF). Collectively, these findings provide new mechanistic insight supporting further exploration of NRG\u20101 as a therapeutic agent for mitigating kidney injury in SCD.<\/jats:p>","DOI":"10.1096\/fj.202504449rr","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:19:42Z","timestamp":1779290382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuregulin\u20101 Mitigates Kidney Injury in Humanized Sickle Cell Mice"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-1976","authenticated-orcid":false,"given":"William K.","family":"Agbozo","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry and Immunology Morehouse School of Medicine  Atlanta Georgia USA"},{"name":"Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences University of Ghana  Accra Ghana"},{"name":"West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), College of Basic and Applied Sciences University of Ghana  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Immunology Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac Joe","family":"Erskine","sequence":"additional","affiliation":[{"name":"Department of Pathology Korle\u2010Bu Teaching Hospital  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia E.","family":"Lekpor","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Immunology Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oguljahan","family":"Babayewa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Immunology Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaijah","family":"Bashi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Immunology Morehouse School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Harbuzariu","sequence":"additional","affiliation":[{"name":"Stem Cell and Organoids Core Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqua","family":"Asberry","sequence":"additional","affiliation":[{"name":"Histology Core, Parker H. 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