Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial fibrosis

Transplant Rev (Orlando). 2008 Jan;22(1):1-5. doi: 10.1016/j.trre.2007.09.004.

Abstract

Chronic allograft tubular atrophy/interstitial fibrosis (TA/IF) is a major cause of late allograft loss. A major challenge to the future of kidney transplantation is to dissect the identifiable causes of chronic allograft TA/IF and to develop cause-specific treatment strategies. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is an important event in native and transplant kidney injury, including chronic allograft TA/IF. During EMT, tubular epithelial cells are transformed into myofibroblasts through a stepwise process including loss of cell-cell adhesion and E-cadherin expression, de novo alpha-smooth muscle actin expression, actin reorganization, tubular basement membrane disruption, cell migration, and fibroblast invasion with production of profibrotic molecules such as collagen types I and III and fibronectin. We examined in this review the molecular and cellular pathways of EMT and their involvement in chronic allograft tubulointerstitial fibrosis. We examined the role of alloimmune T cells and oxidative stress in this context and evaluated EMT as a marker of disease progression. Potential therapeutic options are discussed. In conclusion, there is enough evidence demonstrating that EMT is involved in the pathogenesis of chronic allograft tubulointerstitial fibrosis. However, the extent of its contribution to allograft fibrogenesis remains unknown, and only interventional trials will enable us to clarify this question. Furthermore, additional data are required to determine whether EMT may be used as a surrogate marker of disease progression in kidney transplant recipients.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biomarkers
  • Cadherins / metabolism
  • Cell Adhesion Molecules / metabolism*
  • Epithelial Cells / metabolism
  • Fibroblasts / metabolism
  • Fibrosis / pathology*
  • Gene Expression
  • Graft Rejection
  • Humans
  • Kidney / pathology*
  • Kidney Transplantation / pathology*
  • Mesoderm / metabolism
  • Nephritis, Interstitial / pathology*
  • Risk Factors
  • Signal Transduction
  • Transplantation, Homologous

Substances

  • Biomarkers
  • Cadherins
  • Cell Adhesion Molecules