Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular matrix accumulation in experimental glomerulonephritis

Kidney Int. 1999 Feb;55(2):465-75. doi: 10.1046/j.1523-1755.1999.00275.x.


Background: The evidence that transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of fibrotic diseases is now supported by several lines of investigation. This evidence provides a certain base for targeting TGF-beta as an antifibrotic agent.

Methods: We generated a chimeric cDNA, termed TGF beta RII/Fc, encoding an extracellular domain of the TGF-beta type II receptor fused to the IgG-Fc domain, and tested whether TGF beta RII/Fc could be a novel strategy for treating glomerular diseases.

Results: In cultured BNul-7 cells, recombinant TGF beta RII/Fc reversed the antiproliferative response induced by TGF-beta 1. In addition, TGF beta RII/Fc diminished the TGF-beta 1-induced production of EIIIA-positive fibronectin in cultured normal rat kidney cells. We then introduced the chimeric cDNA into the muscle of the nephritic rats by the hemagglutinating virus of Japan liposome-mediated gene transfer method in order to block the TGF-beta activity in nephritic glomeruli through systemic delivery of chimeric molecules. Treatment with TGF beta RII/Fc gene transfection could suppress the glomerular TGF-beta mRNA in nephritic rats with a comparable effect in the reduction of extracellular matrix accumulation.

Conclusion: TGF beta RII/Fc successfully inhibited the action of TGF-beta in vitro and in vivo, and gene therapy by chimeric TGF beta RII/Fc might be feasible for the therapy of glomerulosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chimera / genetics
  • Extracellular Matrix / metabolism*
  • Feasibility Studies
  • Gene Expression / physiology
  • Genetic Therapy*
  • Glomerular Mesangium / metabolism
  • Glomerular Mesangium / pathology
  • Glomerulonephritis / metabolism
  • Glomerulonephritis / pathology
  • Glomerulonephritis / therapy*
  • Immunoglobulin Fc Fragments / genetics*
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin G / genetics*
  • Immunoglobulin G / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Transforming Growth Factor beta / genetics*
  • Receptors, Transforming Growth Factor beta / metabolism


  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Receptors, Transforming Growth Factor beta