Exosome production and its regulation of EGFR during wound healing in renal tubular cells

Am J Physiol Renal Physiol. 2017 Jun 1;312(6):F963-F970. doi: 10.1152/ajprenal.00078.2017. Epub 2017 Mar 29.


Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing.

Keywords: EGFR; exosomes; kidney; wound healing.

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Benzylidene Compounds / pharmacology
  • Cell Line
  • Epidermal Growth Factor / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism*
  • Exosomes / metabolism*
  • Exosomes / pathology
  • Gefitinib
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism*
  • Kidney Tubules / pathology
  • Mice
  • Polyenes / pharmacology
  • Polyunsaturated Alkamides / pharmacology
  • Quinazolines / pharmacology
  • Signal Transduction
  • Time Factors
  • Wound Healing* / drug effects


  • Aniline Compounds
  • Benzylidene Compounds
  • GW 4869
  • Polyenes
  • Polyunsaturated Alkamides
  • Quinazolines
  • Epidermal Growth Factor
  • EGFR protein, mouse
  • ErbB Receptors
  • manumycin
  • Gefitinib