title: [FTY720 attenuates rat anti-Thy-1 mesangial proliferative glomerulonephritis by inhibition of transforming growth factor β1-connective tissue growth factor pathway].
abstract: OBJECTIVE
  To investigate whether FTY720 inhibits rat mesangial proliferation and extracellular matrix expansion through suppression of transforming growth factor β1-connective tissue growth factor (TGFβ1-CTGF) pathway, and to explore experimental evidence for its effect on mesangial proliferative glomerulonephritis.
  
  
  METHODS
  A rat model of anti-Thy-1 mesangial proliferative glomerulonephritis was established and FTY720 intervention was performed. Periphery blood lymphocyte count, urine protein excretion, glomerular mesangial proliferation, protein and gene expression of TGFβ1 and CTGF and extracellular matrix protein including fibronectin, laminin and collagen IV in isolated glomeruli were documented at 1, 3 and 7 days after injection of anti-Thy-1 antibody.
  
  
  RESULTS
  The model group developed proteinuria at 1, 3 and 7 days after injection of anti-Thy-1 antibody, which were significantly higher [(27.9 ± 7.3), (63.5 ± 18.8) and (52.4 ± 15.4)mg/d, respectively] than those in the control group [(8.4 ± 2.4), (8.4 ± 2.1) and (10.4 ± 3.2) mg/d; respectively, P < 0.01]. FTY720 intervention group showed significantly decreased proteinuria at 3 and 7 days after injection [(31.4 ± 7.0), (25.5 ± 7.7) mg/d, respectively] than model group (P < 0.01), although higher than the control group (P < 0.01). After intervention for 3 and 7 days, FTY720 significantly down-regulated both TGFβ1 and CTGF gene and protein expression in cultured glomeruli, and suppressed the production of glomerular extracellular matrix protein secretion, leading to attenuated mesangial cell proliferation and extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative glomerulonephritis.
  
  
  CONCLUSIONS
  FTY720 significantly attenuates mesangial proliferation and extracellular matrix expansion through inhibition of TGFβ1-CTGF pathway in rat, and thus ameliorates the development of anti-Thy-1 mesangial proliferative glomerulonephritis.
authors.affiliation: Department of Pharmacy, the Central Hospital of Wuhan, Wuhan 430014, China. jjy11170008@yahoo.cn
authors.forename: Jing-yu
authors.initials: JY
authors.lastname: Jiang
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ai-ping
authors.initials: AP
authors.lastname: Deng
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007518:Isoantibodies / Q000276:immunology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D011409:Propylene Glycols / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018800:Thy-1 Antigens / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011409:Propylene Glycols; D018800:Thy-1 Antigens; D053773:Transforming Growth Factor beta1; C035678:anti-Thy antibody; D055513:Connective Tissue Growth Factor; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine