Epithelial-to-mesenchymal transition of human proximal tubular epithelial cells: effects of rapamycin, mycophenolate, cyclosporin, azathioprine, and methylprednisolone

Transplantation. 2007 Mar 27;83(6):809-14. doi: 10.1097/01.tp.0000255680.71816.aa.


Epithelial-to-mesenchymal transition (EMT) of renal proximal tubular epithelial cells (PTEC) into myofibroblasts is an important step in the pathogenesis of chronic allograft nephropathy. The effects of commonly used immunosuppressives in renal transplantation on EMT are not known. PTEC were cultured in transforming growth factor-beta to induce EMT. The effects of the immunosuppressives on cell morphology and alpha-smooth muscle actin were studied by phase contrast microscopy, immunocytochemistry, and western blotting. The effects on versican were studied by [S] labeling and polyacrylamide gel electrophoresis. Rapamycin and mycophenolate mofetil (MMF) prevented EMT and moreover returned myofibroblasts to PTEC morphology. These immunosuppressives also reduced versican production by both PTEC and myofibroblasts. Cyclosporine A, azathioprine, and methylprednisolone were less effective than rapamycin and MMF. Moreover, these immunosuppressives did not decrease versican. Rapamycin and MMF have a greater inhibitory effect on EMT in vitro than older immunosuppressives and may result in less fibrosis and a better long-term allograft survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Azathioprine / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclosporine / pharmacology
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Kidney Transplantation / methods
  • Kidney Tubules, Proximal / cytology*
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism
  • Methylprednisolone / pharmacology
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacology
  • Sirolimus / pharmacology
  • Transforming Growth Factor beta / pharmacology
  • Versicans / metabolism


  • Actins
  • Immunosuppressive Agents
  • Transforming Growth Factor beta
  • Versicans
  • Cyclosporine
  • Mycophenolic Acid
  • Azathioprine
  • Sirolimus
  • Methylprednisolone