title: Lipopolysaccharide-triggered acute aggravation of mesangioproliferative glomerulonephritis through activation of coagulation in a high IgA strain of ddY mice.
abstract: BACKGROUND
  The high IgA (HIGA) strain of ddY mice represents an inbred model of IgA nephropathy that shows mesangioproliferative glomerulonephritis with mesangial IgA deposition. In this study, aggravation of glomerulonephritis in HIGA mice through lipopolysaccharide (LPS)-triggered activation of coagulation was investigated.
  
  
  METHODS
  Twelve-week-old HIGA and BALB/c mice were intraperitoneally injected with LPS twice at an interval of 3 days, and kidney specimens were collected 7 days after the second LPS injection. In an intervention experiment, the factor Xa inhibitor danaparoid was injected intraperitoneally every day for 7 days after the first LPS injection.
  
  
  RESULTS
  LPS injection induced macrophage infiltration and cellular proliferation in the mesangium together with fibrin deposition and monocyte chemoattractant protein 1 mRNA expression, as well as antigen deposition of tissue factor, factor V, factor X, and protease-activated receptor 2. These phenomena were obvious in HIGA mice when compared to BALB/c mice. Interestingly, toll-like receptor 4 was intensely expressed in HIGA mice before LPS injection and subsequently decreased. Danaparoid treatment significantly ameliorated proteinuria, cellular proliferation, and fibrin deposition.
  
  
  CONCLUSIONS
  The present data suggest that tissue factor and factor V induction by LPS may in part accelerate mesangioproliferative glomerulonephritis through activation of factor X and downstream proinflammatory and procoagulant mechanisms.
authors: Division of Molecular Medicine, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka General Hospital, Shizuoka 422-8526, Japan.
authors: Makiko
authors: M
authors: Shimosawa
authors: Koji
authors: K
authors: Sakamoto
authors: Yuki
authors: Y
authors: Tomari
authors: Kohei
authors: K
authors: Kamikado
authors: Hidetaka
authors: H
authors: Otsuka
authors: Ning
authors: N
authors: Liu
authors: Hisayo
authors: H
authors: Kitamura
authors: Kazuhide
authors: K
authors: Uemura
authors: Fumiaki
authors: F
authors: Nogaki
authors: Noriko
authors: N
authors: Mori
authors: Eri
authors: E
authors: Muso
authors: Haruyoshi
authors: H
authors: Yoshida
authors: Takahiko
authors: T
authors: Ono
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000494:pharmacology; D005165:Factor V / Q000235:genetics / Q000378:metabolism; D005170:Factor X / Q000235:genetics / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced* / Q000276:immunology; D006497:Heparan Sulfate / Q000494:pharmacology; D007070:Immunoglobulin A / Q000378:metabolism*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D018932:Chemokine CCL2; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005165:Factor V; D005170:Factor X; D005337:Fibrin; D006497:Heparan Sulfate; D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D018809:Proliferating Cell Nuclear Antigen; D044464:Receptor, PAR-2; D013925:Thromboplastin; D051197:Toll-Like Receptor 4; C495345:TLR4 protein, human; C035838:danaparoid