Mechanisms of Epithelial Repair and Regeneration After Acute Kidney Injury

Semin Nephrol. 2014 Jul;34(4):394-403. doi: 10.1016/j.semnephrol.2014.06.006. Epub 2014 Jun 13.

Abstract

Acute kidney injury (AKI) is a common clinical problem and is associated with high mortality rates. It is accepted that after AKI cellular regeneration of the proximal tubule occurs from intrinsic tubule cells. Recently, scattered tubular cells (STCs) were discovered as a novel subpopulation of tubule cells involved in regeneration. STCs have a distinct morphology, unique protein expression profile resembling that of parietal epithelial cells, proliferate more than the remaining proximal tubule cells, and are less susceptible to injuries. In response to AKI, STCs become more numerous, independent of the primary insult (ischemic, acute obstruction, and so forth). STCs can be detected with the highest sensitivity and manipulated by the parietal epithelial cell-specific, doxycycline inducible transgenic mouse line PEC-rtTA. In cell fate tracing experiments it was shown that STCs are not a fixed progenitor population. Rather, STCs arise from any surviving proximal tubule cell. Thus, the STC phenotype is a transient, graded, and specific transcriptional program facilitating tubular regeneration. Understanding this program my open new approaches to prevent and/or treat AKI.

Keywords: Acute kidney injury; proximal tubular cells; tubular regeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury*
  • Animals
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Epithelial Cells / physiology*
  • Humans
  • Kidney Tubules, Proximal / cytology*
  • Mice
  • Phenotype
  • Regeneration / physiology*