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: Hua Liu, Xin-Ping Zhang, Zhu-Wen Yi
• Journal: Renal failure (Ren Fail) Vol. 35 Issue 10 Pg. 1418-28 ( 2013) ISSN: 1525-6049 [Electronic] England
• PMID: 23991758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccr2 protein, rat
• Chemokine CCL2
• DNA, Antisense
• Isoantibodies
• Receptors, CCR2
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• anti-Thy antibody

Topics

• Animals
• Chemokine CCL2 (antagonists & inhibitors, metabolism)
• DNA, Antisense (therapeutic use)
• Disease Models, Animal
• Female
• Genetic Therapy
• Glomerulonephritis, Membranoproliferative (drug therapy)
• Isoantibodies
• Mesangial Cells (metabolism)
• Proteinuria (drug therapy)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Receptors, CCR2 (metabolism)
• Transforming Growth Factor beta1 (metabolism)