{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:32:51Z","timestamp":1777372371281,"version":"3.51.4"},"reference-count":44,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"crossref","award":["2022J01212, 2024J01560"],"award-info":[{"award-number":["2022J01212, 2024J01560"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Complement activation significantly contributes to the progression of diabetic kidney disease (DKD). Recent studies have shown that renal levels of the complement component 3 (C3) and its receptor (C3aR) increase with disease progression. Mesangial matrix deposition in the glomeruli is an early pathological hallmark of DKD, but the potential role of C3aR in this process remains unclear. In this study, we used C57BLKS\/JGpt wild-type (WT) mice, C57BLKS\/JGpt db\/db mice (a well-established model of type 2 diabetic nephropathy), and a pharmacological C3aR antagonist (C3aRA, SB290157 trifluoroacetate) to investigate this association. Strong C3 and C3aR staining was observed in the glomerular tufts of db\/db mice, with C3aR co-localizing with mesangial nuclear cell markers. After 8 weeks of C3aRA treatment, db\/db mice showed significant improvements in urine albumin-to-creatinine ratio (UACR), glomerular hypertrophy, and mesangial expansion. Inhibition of C3aR suppressed the expression of fibronectin (FN), osteopontin (OPN), and alpha-smooth muscle actin (\u03b1-SMA), indicating reduced mesangial matrix deposition. C3aRA also decreased renal deposition of calcineurin (CaN) and nuclear factor of activated T-cells 1 (NFATc1). These findings indicate a potential association between C3aR signaling and phenotypic and functional alterations in mesangial cells, which may be linked to the CaN\/NFATc1 pathway. Given the well-documented pharmacological limitations of SB290157, our results do not confirm a definitive regulatory role for C3aR, but identify C3aR as a candidate mediator of mesangial matrix deposition in DKD, providing preliminary evidence that targeting C3aR may represent a potential therapeutic strategy for diabetic kidney disease.<\/jats:p>","DOI":"10.7717\/peerj.21248","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T08:52:56Z","timestamp":1777366376000},"page":"e21248","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological targeting of C3aR modulates mesangial matrix deposition in db\/db mice"],"prefix":"10.7717","volume":"14","author":[{"given":"Jing","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengjie","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6733-0472","authenticated-orcid":true,"given":"Jianxin","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China"},{"name":"Department of 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