Gene transfer targeting interstitial fibroblasts by the artificial viral envelope-type hemagglutinating virus of Japan liposome method

Background Tubulointerstitial inflammation and fibrosis are commonly associ ated with most human glomerular diseases. The degree of tubulointerstitial damage, rather than the glomerular injury, could correlate with the degree of renal functional impairment and accurately predict long-term prognosis. In an effort to understand the pathogenesis of the progressive interstitial fibrosis, we developed a new strategy of gene transfer to the interstitial fibroblasts. Methods. Either fluorescein isothiocyanate (FITC)-labeled oligodeoxynucleot ides (ODNs) or pEBAct-NlacF expression vector was introduced into the kidne y of normal rats retrogradely via ureter by using the artificial viral enve lope (AVE)type hemagglutinating virus of Japan (HVJ) liposome method. Results. FITC-labeled ODNs were accumulated diffusely in the nuclei of the interstitial cells in the transfected kidney 10 minutes after transfection, and the interstitial cells were identified as interstitial fibroblasts by immunostaining with ER-TR7. To examine the gene expression in the interstit ium, pEBAct-NlacF gene-conjugated HVJ liposome was injected retrogradely th rough the ureter, and in consequence, nuclear P-galactosidase activity was continuously observed in interstitial cells at least two weeks after transf ection. Conclusion. This new strategy of gene transfer to the interstitial fibrobla sts is useful for the investigation of the pathophysiology of tubulointerst itial lesion, and furthermore, it may be a promising new therapeutic method for the progression of interstitial fibrosis.