title: Epithelial-mesenchymal transition in renal fibrosis - evidence for and against.
abstract: Epithelial to mesenchymal transition (EMT) is a well established biological process in metazoan embryological development. Over the past 15 years, investigators have sought to establish whether EMT also occurs in renal epithelial cells, following kidney injury, and to show that the mesenchymal cells formed could give rise to myofibroblasts which populate the renal interstitium, causing fibrosis within it. There is no doubt that proximal tubular epithelial cells (PTECs) can undergo EMT in vitro in response to TGFβ-1 and other inflammatory stimuli. Moreover, the results of experiments with animal models of renal fibrosis and examination of biopsies from patients with chronic kidney disease have lent support to the hypothesis that EMT occurs in vivo. This review discusses some of the key evidence underlying that idea and summarises recent advances in understanding the molecular mechanism underlying the process. Early experiments using mice which were genetically engineered to mark PTECs with the LacZ gene to trace their fate following kidney injury provided evidence supporting the occurrence of EMT. Recently, however, cell lineage tracking experiments using the red fluorescent protein (RFP) as a high-resolution marker for cells of renal epithelial origin did not replicate this result; the interstitial space following kidney injury was devoid of RFP expressing cells, leading the investigators to reject the renal EMT hypothesis.
authors.affiliation: Imperial College Kidney and Transplant Institute, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Fragiadaki
authors.forename: Roger M
authors.initials: RM
authors.lastname: Mason
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology*; D051379:Mice