Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial fibrosis

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 out 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 α-smooth muscle actin (α-SMA) expression, actin reorganization, tubular basement membrane disruption, cell migration and fibroblast invasion with production of profibrotic molecules such as collagen type I and III, and fibronectin. This review examines 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.

Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype

“…Lung fibroblasts can be derived from fibroblasts in situ or from the recruitment of circulating precursors in the site of inflammation. Recent studies suggest that EMT is implicated during the development of BO [29,30,155,156], as has been demonstrated for chronic kidney rejection [157][158][159][160]. A study with biopsies and ex vivo cultures from lung transplant recipients showed that BEC expressed S100A4 [30].…”

Proximal tubular dysfunction as an indicator of chronic graft dysfunction

“…We have observed an inverse developmental transition associated with graft fibrosis, namely an epithelial-to-mesenchymal transition (EMT). EMT is a process whereby fully differentiated epithelial cells undergo transition to a mesenchymal phenotype giving rise to fibroblasts and myofibroblasts (12)(13)(14).…”

Heat Shock Protein 27(HSP27) in Kidney Disease: Potentials for Diagnosis and Therapy

“…During EMT, tubular epithelial cells are gradually changed into myofibroblasts. [62][63][64] HSP27 produces its cytoprotective achieve through modulation of the actin cytoskeleton in addition to inhibition of OS and apoptosis. [65][66][67] It also plays a role in inflammation, cell signaling, differentiation as well as proliferation.…”