Epithelial-mesenchymal transition of renal tubules: divergent processes of repairing in acute or chronic injury?

Epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs) is commonly considered as the major mechanism leading to renal fibrosis in chronic kidney diseases (CKD) injury. We raise the hypothesis that EMT in adult kidney may be an event of "atavistic" phenotypic transition, which mimics but reverses the genetic and cellular processes of development of renal tubules. Transformed TECs may be regarded as induced mesenchymal stem-like cells, representing a cellular self-adaptation when in acute or chronic injury. The reasons are as follows: (1) Embryonic gene WT1 and Pax2, which govern tubule development, have been found to re-express during tubular EMT when facing injury. (2) The common factors that induce EMT in vitro, like IL-1, angiotension II and hypoxia could also promote WT1 and/or Pax2 re-expression. (3) Expression of WT1 and Pax2 are found to be associated with progenitor cells. (4) Beside embryonic gene WT1 and Pax2, we also found that some stem cell markers like CD133 were expressed during EMT process. (5) The process of EMT is not only take place in chronic kidney injury (CKD), but also in acute kidney injury (AKI) as well. (6) The phenotype transition of TECs and genetic event during AKI are entirely consistent with what happened in CKD, but the outcome is completely different. Thus, we thought tubular injury of CKD and AKI may share a common initiative repair mechanism: tubular EMT, that is TECs are transformed into induced mesenchymal stem-like cells, and then interpret the injurious signal differently in acute versus chronic conditions, so as to possess a divergent fates, tubular regeneration or fibrosis formation, depending on a different microenvironment or the duration of the injury. In this sense, tubular EMT could be purposefully orientated into a constructively pathway that repair kidney injury via tubular regeneration, matrix remodeling and tissue structure and function restoration.