Objective: To investigate the effect of endothelin-1 (ET-1) on mesangial cells(MC) proliferation and mesangial matrix expansion in vivo.
Methods: Antisense oligodeoxynucleotide(As-ODN) and its control sequences, sense oligodeoxynucleotide(Se-ODN) and mismatch oligodeoxynucleotide(Mis-ODN), targeting pre-proendothelin-1 mRNA (ppET-1) were delivered into the kidney of rats with mesangioproliferative glomerulonephritis (MsPGN) model respectively at day 2 by lipofectin-mediated gene transfer method. The efficiency of transfer of ODNs into MC was examined with biotinylated As-ODN staining. Four days after the rats were sacrificed, the influence of ODNs on ET-1 production by glomeruli was tested with radioimmunoassay(RIA). The action of ODNs on MC proliferation and mesangial matrix expansion was evaluated with quantitative pathologic analysis.
Results: ODNs were transferred into MC in vivo. The glomerular ET-1 production was decreased by As-ODN [(32 +/- 19) ng/g, P < 0.05] with reduction of mesangial cell proliferation [(0.82 +/- 0.04)/100 micron 2, P < 0.05] and mesangial matrix expansion[(12.8 +/- 1.6)%, P < 0.05], where Se-ODN and Mis-ODN did not show any effect on all of these.
Conclusions: Specific inhibition of ET-1 gene expression leads to reduction of proliferation of mesangial cell and expansion of mesangial matrix in rats with MsPGN model. ET-1 is one of the important inflammatory mediators which can stimulate MC proliferation and mesangial matrix expansion in vivo.