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Most patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN) with severe kidney manifestations. Renal fibrosis can be primarily attributed to overproliferation of mesangial cells (MCs), which are subject to drug treatment. Nevertheless, the detailed mechanisms remain elusive. We sought to identify the effect of cyclophosphamide (CTX), a drug commonly used for LN treatment, on MC proliferation and explore its underlying mechanisms. Material\/Methods. Cell proliferation and fibrosis in mouse kidney tissues were determined by histopathology staining techniques. Flow cytometry was used for cell cycle analysis. Cell cycle regulators were examined in vitro following treatment of immortalized human MCs with platelet-derived growth factor subunit B (PDGF-B). Quantitative real-time PCR and western blot analyses were used to measure the mRNA and protein levels of candidate cell cycle regulators, respectively. Results. CTX inhibited cell overproliferation induced by platelet-derived growth factor subunit B in vitro and in vivo. CTX (40\u2009mg\/l) was sufficient to induce G0\/G1 phase cell cycle arrest. CTX treatment downregulated many critical cell cycle regulators including cyclins and cyclin-dependent kinases but upregulated cyclin-dependent kinase inhibitors. Additionally, CTX-treated samples showed significantly reduced fibrosis, as indicated by lower expression of interleukin-1\u03b2 and \u03b1-smooth muscle actin. Conclusion. CTX inhibits proliferation of MCs by modulating cell cycle regulator and therefore arresting them at G1 phase. CTX treatment significantly alleviates the severity of renal fibrosis. These findings provide novel insights into the mechanisms by which CTX affects LN.<\/jats:p>","DOI":"10.1155\/2021\/3803601","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T23:20:20Z","timestamp":1637018420000},"page":"1-9","source":"Crossref","is-referenced-by-count":7,"title":["Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression"],"prefix":"10.1155","volume":"2021","author":[{"given":"Yuehong","family":"Ma","sequence":"first","affiliation":[{"name":"Shanxi Key Laboratory of Kidney Disease, Department of Nephrology, Shanxi Provincial People\u2019s Hospital, Taiyuan, China"},{"name":"Shanxi Precision Medicine Center, Shanxi Provincial People\u2019s Hospital, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Fang","sequence":"additional","affiliation":[{"name":"Shanxi Institute of Scientific and Technical Information, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Kidney Disease, Department of Nephrology, Shanxi Provincial People\u2019s Hospital, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Shanxi Provincial People\u2019s Hospital, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7500-0959","authenticated-orcid":true,"given":"Yafeng","family":"Li","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Kidney Disease, Department of Nephrology, Shanxi Provincial People\u2019s Hospital, Taiyuan, China"},{"name":"Shanxi Precision Medicine Center, Shanxi Provincial People\u2019s Hospital, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8082-4389","authenticated-orcid":true,"given":"Rongshan","family":"Li","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Kidney Disease, Department of Nephrology, Shanxi Provincial People\u2019s Hospital, Taiyuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.365"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.45.1.525"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05780616"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1002\/art.39594"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.02.025"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.229"},{"issue":"1","key":"7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12950-019-0227-x","article-title":"Mesangial cells are key contributors to the fibrotic damage seen in the lupus nephritis glomerulus","volume":"16","author":"R. 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