title: Epithelial-mesenchymal-epithelial cycling in kidney repair.
abstract: OBJECTIVE
  Tubule repair following acute kidney injury involves epithelial de-differentiation followed by cell migration and proliferation and eventual re-differentiation. This review describes our understanding of how that process is regulated.
  
  
  RESULTS
  Epithelial de-differentiation after kidney injury or in epithelial culture systems is controlled by secreted factors such as transforming growth factor beta and hepatocyte growth factor as well as cell-cell and cell-matrix interactions. These surface signals stimulate intracellular signaling via the mitogen-activated protein kinase, phosphoinositide-3-kinase, and Wnt/beta-catenin pathways that in turn activate the morphologic and transcriptional events involved in cell spreading, migration, and proliferation. As cell confluency increases during the repair process, and the factors stimulating de-differentiation are suppressed, these morphogenic programs are downregulated and signals to promote re-differentiation are activated.
  
  
  CONCLUSIONS
  This review focuses on the underlying molecular mechanism of epithelial de-differentiation and re-differentiation in tubule repair in vivo and formation in vitro, thus giving insight into possible strategies for improving recovery following acute kidney injury and preventing progression to chronic kidney disease.
authors.affiliation: Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. Shuta.Ishibe@Yale.edu
authors.forename: Shuta
authors.initials: S
authors.lastname: Ishibe
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Cantley
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004848:Epithelium / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000254:growth & development / Q000502:physiology; D008648:Mesoderm / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D051153:Wnt Proteins