Dedifferentiation and Redifferentiation in Epithelial Repair

M. A. Hallman, R. G. Schnellmann

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Acute kidney injury (AKI) occurs in up to 30% of hospitalized patients in intensive care units and independently predicts a mortality rate of approximately 40%. Most frequently, AKI results from acute tubular necrosis following hypoperfusion of the renal proximal tubular (RPT) epithelium. Regeneration following AKI is mediated by surviving RPT cells (RPTC) that dedifferentiate, proliferate, migrate, and redifferentiate to restore the damaged epithelial monolayer. Growth factors are required for all four phases of regeneration; however, their regulation of dedifferentiation/redifferentiation is not fully understood. Dedifferentiation is characterized by loss of apical-basal polarity and the brush border, formation of stress fibers, elongated cell morphology, and expression of mesenchymal proteins. Activation of several signal transduction pathways by growth factors, including transforming growth factor-?, epidermal growth factor, and fibroblast growth factor-2, mediates the phenotypic changes of dedifferentiation. The mechanism of RPTC redifferentiation is largely unexplored. The current literature suggests that several growth factors including bone morphogeneic protein-7, collagen IV, and hepatocyte growth factor mediate redifferentiation through negative regulation of signal transduction pathways that drive and maintain dedifferentiation.

Original languageEnglish (US)
Title of host publicationRenal Toxicology
PublisherElsevier Inc.
Pages151-167
Number of pages17
Volume7
ISBN (Print)9780080468686
DOIs
StatePublished - Aug 12 2010
Externally publishedYes

Keywords

  • ? integrins
  • Apical-basal polarity
  • Bone morphogenic protein-7
  • Collagen IV
  • E-cadherin
  • Epidermal growth factor
  • Epidermal growth factor receptor
  • Fibroblast growth factor-2
  • Hepatocyte growth factor
  • N-cadherin
  • Stress fibers
  • Transforming growth factor-?
  • Vimentin

ASJC Scopus subject areas

  • Medicine(all)

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