title: Efficacy of antisense monocyte chemoattractant protein-1 (MCP-1) in a rat model of mesangial proliferative glomerulonephritis.
abstract: OBJECTIVE
  The effects of inhibition of monocyte chemoattractant protein-1 (MCP-1) on a rat model of mesangial proliferative glomerulonephritis (MsPGN) were evaluated.
  
  
  METHODS
  The anti-Thy-1 MsPGN model was developed by intravenously injecting anti-Thy-1 monoclonal antibodies into rats, followed by an injection of mesangial cells transfected with antisense MCP-1 into the renal artery. Exogenous cells were detected by in situ hybridization. Rats (40 total) were randomly divided into five groups: SO (sham operation), TG (Thy-1 glomerulonephritis model), MC (non-transfected normal rat mesangial cell), BC (pLXSN empty vector or blank control), and AM (antisense MCP-1 transfection) groups. Effects of exogenous MCP-1 on urinary protein excretion rate, biochemical parameters, and pathological changes were evaluated. Expression of MCP-1 and transforming growth factor-β1 (TGF-β1) were detected by immunohistochemistry. mRNA expression of MCP-1, TGF-β1, and CC chemokine receptor 2 (CCR2) were detected by RT-PCR.
  
  
  RESULTS
  Exogenous MCP-1 cDNA was successfully transfected into mesangial cells. Exogenous mesangial cells were detected in glomeruli by in situ hybridization. Glomerular mesangial cell proliferation, 24-h urinary protein excretion rate, mRNA expression of MCP-1, TGF-β1, and CCR2, and protein expression of MCP-1 all decreased in the AM group as compared to the control group (p < 0.05), but there was no significant difference in the expression level of TGF-β1 protein.
  
  
  CONCLUSIONS
  (1) Mesangial cells can be used as a vector to transfect exogenous genes into kidneys; (2) antisense MCP-1 decreases mesangial cell proliferation and pathological injury in MsPGN model rats by decreasing expression of MCP-1 and CCR2; and (3) antisense MCP-1 suppressed mesangial cell proliferation and matrix accumulation in anti-Thy-1 MsPGN model rats, which did not entirely depend on TGF-β1.
authors.affiliation: Division of Pediatric Nephrology, The Children's Medical Center, The Second Xiangya Hospital, Central South University , Changsha , China and.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Zhang
authors.forename: Zhu-Wen
authors.initials: ZW
authors.lastname: Yi
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016373:DNA, Antisense / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy*; D007518:Isoantibodies; D050527:Mesangial Cells / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D016373:DNA, Antisense; D007518:Isoantibodies; D054390:Receptors, CCR2; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C035678:anti-Thy antibody