title: Artemisinin analogue SM934 ameliorates the proteinuria and renal fibrosis in rat experimental membranous nephropathy.
abstract: OBJECTIVE
  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-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.
  
  
  CONCLUSIONS
  SM934 ameliorates kidney injury and attenuates the tubulointerstitial fibrosis in PHN rats by down-regulation of the TGF-β1/Smad signaling pathway.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Tian-tian
authors.initials: TT
authors.lastname: Li
authors.affiliation: Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jing-feng
authors.initials: JF
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiao-qian
authors.initials: XQ
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Feng-hua
authors.initials: FH
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: 1] State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2] Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Zuo
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D005355:Fibrosis / Q000188:drug therapy*; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D023421:Models, Animal; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D037621:Artemisinins; C550182:beta-aminoarteether maleate; C031327:artemisinin