Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression

Objectives. 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 remai...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yuehong Ma, Ling Fang, Rui Zhang, Peng Zhao, Yafeng Li, Rongshan Li
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/198043f3fa6f44c687756c69e42edfd3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:198043f3fa6f44c687756c69e42edfd3
record_format	dspace
spelling	oai:doaj.org-article:198043f3fa6f44c687756c69e42edfd32021-11-29T00:56:45ZCyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression1875-863010.1155/2021/3803601https://doaj.org/article/198043f3fa6f44c687756c69e42edfd32021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/3803601https://doaj.org/toc/1875-8630Objectives. 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 mg/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-1β and α-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.Yuehong MaLing FangRui ZhangPeng ZhaoYafeng LiRongshan LiHindawi LimitedarticleMedicine (General)R5-920ENDisease Markers, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yuehong Ma Ling Fang Rui Zhang Peng Zhao Yafeng Li Rongshan Li Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression
description	Objectives. 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 mg/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-1β and α-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.
format	article
author	Yuehong Ma Ling Fang Rui Zhang Peng Zhao Yafeng Li Rongshan Li
author_facet	Yuehong Ma Ling Fang Rui Zhang Peng Zhao Yafeng Li Rongshan Li
author_sort	Yuehong Ma
title	Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression
title_short	Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression
title_full	Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression
title_fullStr	Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression
title_full_unstemmed	Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression
title_sort	cyclophosphamide attenuates fibrosis in lupus nephritis by regulating mesangial cell cycle progression
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/198043f3fa6f44c687756c69e42edfd3
work_keys_str_mv	AT yuehongma cyclophosphamideattenuatesfibrosisinlupusnephritisbyregulatingmesangialcellcycleprogression AT lingfang cyclophosphamideattenuatesfibrosisinlupusnephritisbyregulatingmesangialcellcycleprogression AT ruizhang cyclophosphamideattenuatesfibrosisinlupusnephritisbyregulatingmesangialcellcycleprogression AT pengzhao cyclophosphamideattenuatesfibrosisinlupusnephritisbyregulatingmesangialcellcycleprogression AT yafengli cyclophosphamideattenuatesfibrosisinlupusnephritisbyregulatingmesangialcellcycleprogression AT rongshanli cyclophosphamideattenuatesfibrosisinlupusnephritisbyregulatingmesangialcellcycleprogression
_version_	1718407632130146304

Cyclophosphamide Attenuates Fibrosis in Lupus Nephritis by Regulating Mesangial Cell Cycle Progression

Ejemplares similares