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Although sublytic C5b-9 has been reported to affect pro-inflammatory cytokine expression in glomerular mesangial cells (GMCs), the induction of other pro-inflammatory mediators remains unclear. In this study, we demonstrated that SET and MYND domain-containing protein 4 (SMYD4), SRY-related HMG-box gene 7 (SOX7), S100 calcium-binding protein A8 (S100A8), and S100A9 were overexpressed in the renal tissues of Thy-1N rats and in the GMCs stimulated by sublytic C5b-9. Mechanistically, SOX7 triggered S100A8\/A9 gene transcription through binding to S100A8 promoter (+21 to\u00a0+31\u00a0nt) and S100A9 promoter (\u22121698 to \u22121688\u00a0nt), and SMYD4 mediated SOX7 methylation at K159, a new methylation site, enhancing SOX7 function and S100A8\/A9 transcription. The animal experiments confirmed that silencing SMYD4, SOX7, or S100A8\/A9 gene could inhibit GMC proliferation, extracellular matrix accumulation, and proteinuria in Thy-1N rats. Moreover, silencing SMYD4 gene could inhibit renal SOX7-K159me2\/3, and silencing SMYD4 or SOX7 gene could inhibit renal S100A8\/A9 production. Meanwhile, the SOX7-K159 methylation inhibitory peptide exhibited the similar intervention effects as SMYD4 and SOX7 knockdown in Thy-1N rats. In addition, the expression levels of SMYD4, SOX7, SOX7-K159me2\/3, and S100A8\/A9 all increased in the renal tissues of MsPGN patients. Collectively, our findings suggest that SMYD4-mediated SOX7-K159me2\/3 partly contributes to sublytic C5b-9-induced S100A8\/A9 expression in Thy-1N rats, which provides a novel insight into human MsPGN pathogenesis.<\/jats:p>","DOI":"10.1093\/jmcb\/mjag003","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:46:19Z","timestamp":1770900379000},"source":"Crossref","is-referenced-by-count":1,"title":["Sublytic C5b-9 induces S100A8\/A9 expression via SMYD4-dependent SOX7-K159 methylation in the glomerular mesangial cells of Thy-1 nephritis rats"],"prefix":"10.1093","volume":"18","author":[{"given":"Yajuan","family":"Gong","sequence":"first","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]},{"name":"Central Laboratory, the First Hospital of Anhui University of Science and Technology , Huainan 232000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Peng","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Dong","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Jiangning Hospital of Nanjing Medical University Department of Nephrology, , Nanjing 211100 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjin","family":"Liao","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]},{"name":"Key Laboratory of Antibody Technology of Ministry of Health, Nanjing Medical University , Nanjing 211166 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]},{"name":"Key Laboratory of Antibody Technology of Ministry of Health, Nanjing Medical University , Nanjing 211166 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Qiu","sequence":"additional","affiliation":[{"name":"Nanjing Medical University Department of Immunology, Key Laboratory of Immunological Environment and Disease, , Nanjing 211166 ,","place":["China"]},{"name":"Immune Cells Translational Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University , Nanjing 211100 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"2026101308370504700_bib1","doi-asserted-by":"crossref","first-page":"e15158","DOI":"10.1111\/exd.15158","article-title":"An overview of S100 proteins and their functions in skin homeostasis, interface dermatitis conditions and other skin pathologies","volume":"33","author":"Abdi","year":"2024","journal-title":"Exp. 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