Introduction of DNA enzyme for Egr-1 into tubulointerstitial fibroblasts by electroporation reduced interstitial alpha-smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats

Gene Ther. 2002 Apr;9(8):495-502. doi: 10.1038/


The phenotypic alteration of interstitial fibroblasts into 'myofibroblasts', acquiring characteristics of both fibroblasts and smooth muscle cells is a key event in the formation of tubulointerstitial fibrosis. The up-regulation of the early growth response gene 1 (Egr-1) preceded the increased interstitial expression of alpha-smooth muscle actin (alphaSMA), a marker of phenotypic changes, in obstructed kidney, a model of interstitial fibrosis. To target Egr-1 expression in the interstitium of obstructed kidneys, we introduced a DNA enzyme for Egr-1 (ED5) or scrambled DNA (SCR) into interstitial fibroblasts by electroporation-mediated gene transfer. Northern blot analysis confirmed an increase in the cortical mRNA expression of Egr-1 in the obstructed kidneys from untreated or SCR-treated rats, while ED5 transfection blocked Egr-1 expression with a concomitant reduction in TGF-beta, alphaSMA and type I collagen mRNA expression. Consequently, ED5 inhibited interstitial fibrosis. In conclusion, electroporation-mediated retrograde gene transfer can be an ideal vehicle into interstitial fibroblasts, and molecular intervention of Egr-1 in the interstitium may become a new therapeutic strategy for interstitial fibrosis.

MeSH terms

  • Actins / genetics
  • Animals
  • Cell Line
  • Collagen Type I / genetics
  • DNA, Single-Stranded / genetics*
  • DNA-Binding Proteins / genetics*
  • Early Growth Response Protein 1
  • Electroporation
  • Fibrosis
  • Gene Expression
  • Genetic Therapy / methods*
  • Immediate-Early Proteins*
  • Kidney / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Transcription Factors / genetics*
  • Transforming Growth Factor beta / genetics
  • Ureteral Obstruction / therapy*


  • Actins
  • Collagen Type I
  • DNA enzyme ED5
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Immediate-Early Proteins
  • RNA, Messenger
  • Transcription Factors
  • Transforming Growth Factor beta