Ex vivo transfer of the decorin gene into rat glomerulus via a mesangial cell vector suppressed extracellular matrix accumulation in experimental glomerulonephritis

The activation of transforming growth factor-beta (TGF-beta) is known to be one of the major causes of glomerulosclerosis. Decorin (DCN) is a natural inhibitor of TGF. The purpose of this study was to assess the feasibility of transferring the DCN gene to antithymocyte serum (ATS) glomerulonephritis glomeruli via a mesangial cell vector to treat glomerulonephritis fibrosis. For this process, the recombinant eukaryotic expression plasmid pcDNA3.1A-DCN was constructed and transfected into mesangial cell. The DCN-positive cloned cells were transferred to rat antithymocyte serum glomeruli by a left renal artery injection. Using immunohistochemical staining, approximately 37-60% (48.6% +/- 11.34%; mean +/- SE, n = 8) of the glomeruli were BrdU-positive in the injected-side kidney. DCN proteins were observed in the cytoplast beginning 12 h after injection. TGF-beta1 expression in the injected side glomeruli decreased significantly at day 4 (P < 0.05), compared with that in the uninjected-side kidney. The expression leaves of fibronectin and collagen IV decreased significantly at days 1-2 (P < 0.01) and day 4 (fibronectin, P < 0.01; collagen IV, P < 0.05). These results suggest that the use of DCN can decrease antithymocyte serum glomerulonephritis extracellular matrix (ECM) ingredients and that such use offers a favorable experimental basis for gene therapy for kidney disease. (C) 2004 Elsevier Inc. All rights reserved.