Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy

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...

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Published in:Acta pharmacologica Sinica 2015-02, Vol.36 (2), p.188-199
Main Authors: Li, Tian-tian, Zhang, Xiao-hui, Jing, Jing-feng, Li, Xin, Yang, Xiao-qian, Zhu, Feng-hua, Tang, Wei, Zuo, Jian-ping
Format: Article
Language:English
Subjects:
Animals
Artemisinins - pharmacology
Biomedical and Life Sciences
Biomedicine
Fibrosis - drug therapy
Glomerulonephritis, Membranous - drug therapy
Immunology
Internal Medicine
Kidney - drug effects
Kidney Diseases - drug therapy
Male
Medical Microbiology
Models, Animal
Original
original-article
Pharmacology/Toxicology
Proteinuria - drug therapy
Rats
Rats, Sprague-Dawley
SD大鼠
Vaccine
实验性
肾小球肾炎
肾病
肾间质纤维化
腹膜
蛋白尿
青蒿素
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cited_by cdi_FETCH-LOGICAL-c477t-e381e39ae25765ca63f3d91d5445a0743b3efc321217ccf01c581564a849830b3
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container_title Acta pharmacologica Sinica
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Tang, Wei
Zuo, Jian-ping
description 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-FxlA 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- β1 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- β1/Smad signaling pathway.
doi_str_mv 10.1038/aps.2014.134
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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- β1/Smad signaling pathway.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/aps.2014.134</identifier><identifier>PMID: 25619396</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Artemisinins - pharmacology ; Biomedical and Life Sciences ; Biomedicine ; Fibrosis - drug therapy ; Glomerulonephritis, Membranous - drug therapy ; Immunology ; Internal Medicine ; Kidney - drug effects ; Kidney Diseases - drug therapy ; Male ; Medical Microbiology ; Models, Animal ; Original ; original-article ; Pharmacology/Toxicology ; Proteinuria - drug therapy ; Rats ; Rats, Sprague-Dawley ; SD大鼠 ; Vaccine ; 实验性 ; 肾小球肾炎 ; 肾病 ; 肾间质纤维化 ; 腹膜 ; 蛋白尿 ; 青蒿素</subject><ispartof>Acta pharmacologica Sinica, 2015-02, Vol.36 (2), p.188-199</ispartof><rights>CPS and SIMM 2015</rights><rights>Copyright Nature Publishing Group Feb 2015</rights><rights>Copyright © 2015 CPS and SIMM 2015 CPS and SIMM</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-e381e39ae25765ca63f3d91d5445a0743b3efc321217ccf01c581564a849830b3</citedby><cites>FETCH-LOGICAL-c477t-e381e39ae25765ca63f3d91d5445a0743b3efc321217ccf01c581564a849830b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/95561A/95561A.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326791/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326791/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25619396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Tian-tian</creatorcontrib><creatorcontrib>Zhang, Xiao-hui</creatorcontrib><creatorcontrib>Jing, Jing-feng</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Yang, Xiao-qian</creatorcontrib><creatorcontrib>Zhu, Feng-hua</creatorcontrib><creatorcontrib>Tang, Wei</creatorcontrib><creatorcontrib>Zuo, Jian-ping</creatorcontrib><title>Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim： SM934 is a novel water-soluble artemisinin derivative with immunoregulatory activities that has been used to treat murine lupus nephritis. 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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-FxlA 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- β1 expression and Smad2/3 phosphorylation, and increased Smad7 expression in the kidneys. 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subjects Animals
Artemisinins - pharmacology
Biomedical and Life Sciences
Biomedicine
Fibrosis - drug therapy
Glomerulonephritis, Membranous - drug therapy
Immunology
Internal Medicine
Kidney - drug effects
Kidney Diseases - drug therapy
Male
Medical Microbiology
Models, Animal
Original
original-article
Pharmacology/Toxicology
Proteinuria - drug therapy
Rats
Rats, Sprague-Dawley
SD大鼠
Vaccine
实验性
肾小球肾炎
肾病
肾间质纤维化
腹膜
蛋白尿
青蒿素
title Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy
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