Targeting of plasmid DNA to renal interstitial fibroblasts by cationized gelatin

Renal interstitial fibrosis is the common pathway of chronic renal disease, while it causes end-stage renal failure. A lot of cytokines and biologically active substances are well recognized to be the candidates of primary mediators to induce accumulation of extracelluar matrix (ECM) in the interstitial fibrotic area. Interstitial fibroblasts are played a crucial role in the accumulation of excess ECM during renal interstitial fibrogenesis. Therefore, the targeting of therapeutic drugs and genes to interstitial renal fibroblasts is effective in suppressing the progress of interstitial renal failure. However, despite various approaches and techniques, few successful results have been reported on the in vivo targeting for interstitial fibroblasts. The objective of this study is to deliver an enhanced green fluorescent protein (EGFP) plasmid DNA, as a model plasmid DNA, into renal interstitial space by a cationized gelatin. After the plasmid DNA with or without complexation of the cationized gelatin was injected to the left kidney of mice via the ureter, unilateral ureteral obstruction (UUO) was performed for the mice injected to induce the renal interstitial fibrosis. When the EGFP plasmid DNA complexed with the cationized gelatin was injected, EGFP expression was observed in the fibroblasts in the interstitial area of renal cortex. It is concluded that the retrograde injection of EGFP plasmid DNA complexed with the cationized gelatin is available to target the interstitial renal fibroblasts which are currently considered as the cell source responsible for excessive ECM synthesis.