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Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy
文献类型：期刊论文
| 作者 | Li, Tian-tian1; Zhang, Xiao-hui2; Jing, Jing-feng1; Li, Xin1; Yang, Xiao-qian1; Zhu, Feng-hua1; Tang, Wei1 ; Zuo, Jian-ping1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2015-02 |
| 卷号 | 36期号:2页码:188-199 |
| 关键词 | SM934 artemisinin prednisolone membranous nephropathy passive Heymann nephritis proteinuria podocyte renal fibrosis TGF beta 1 Smad epithelial-mesenchymal transition |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2014.134 |
| 文献子类 | Article |
| 英文摘要 | Aim: SM934 is a novel water-soluble artemisinin derivative with immunoregulatory activities that has been used to treat murine lupus nephritis. In the current study, we investigated the effects of SM934 on rat experimental membranous nephropathy. Methods: Passive Heymann nephritis (PHN) was induced in SD rats by intraperitoneal injection of anti-Fx1A serum. The rats were orally administered SM934 (12.5 and 25 mg.kg(-1).d(-1)) or prednisolone (5 mg.kg(-1).d(-1)) for 28 d. Blood and urine sample, and kidney tissue were collected for analyses. Human complement C3a-induced injury of HK-2 cells was used for in vitro experiments. Results: Treatment of PHN rats with SM934 or prednisolone attenuated the progression of glomerulonephritis and renal fibrosis, as evidenced by the reduced level of proteinuria and circulating antibodies, as well as by the reduced immune complex deposition, reversed podocyte injuries, and attenuated tubulointerstitial fibrosis in the kidneys. Furthermore, the two drugs suppressed TGF-beta 1 expression and Smad2/3 phosphorylation, and increased Smad7 expression in the kidneys. The two doses of SM934 produced almost identical therapeutic effects on PHN rats. Pretreatment with SM934 or a C3a receptor antagonist blocked the C3a-induced epithelial-mesenchymal transition in HK-2 cells in vitro. Conclusion: SM934 ameliorates kidney injury and attenuates the tubulointerstitial fibrosis in PHN rats by down-regulation of the TGF-beta 1 Smad signaling pathway. |
| WOS关键词 | CISPLATIN-INDUCED NEPHROTOXICITY ; TUBULAR EPITHELIAL-CELLS ; HEYMANN NEPHRITIS ; MESENCHYMAL TRANSITION ; TGF-BETA ; EXPRESSION ; INJURY ; GLOMERULONEPHRITIS ; INFLAMMATION ; MECHANISM |
| 资助项目 | National Natural Science Foundation of China (NSFC)[81273524] ; National Natural Science Foundation of China (NSFC)[81322049] ; National Natural Science Foundation of China (NSFC)[81273525] ; National Science & Technology Major Project "New Drug Creation and Manufacturing Program", China[2014ZX09101002] ; National Key Basic Research Programme (973 Programme)[2014CB541906] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5351051 |
| WOS记录号 | WOS:000349333700005 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276655]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Tang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Tian-tian,Zhang, Xiao-hui,Jing, Jing-feng,et al. Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy[J]. ACTA PHARMACOLOGICA SINICA,2015,36(2):188-199. |
| APA | Li, Tian-tian.,Zhang, Xiao-hui.,Jing, Jing-feng.,Li, Xin.,Yang, Xiao-qian.,...&Zuo, Jian-ping.(2015).Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy.ACTA PHARMACOLOGICA SINICA,36(2),188-199. |
| MLA | Li, Tian-tian,et al."Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy".ACTA PHARMACOLOGICA SINICA 36.2(2015):188-199. |
入库方式： OAI收割
来源：上海药物研究所
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