Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately

Stem Cell Res Ther. 2015 Jun 16;6(1):120. doi: 10.1186/s13287-015-0103-4.


Introduction: Wnt and Notch signaling pathways are critically involved in relative cell fate decisions within the development of cutaneous tissues. Moreover, several studies identified the above two pathways as having a significant role during wound healing. However, their biological effects during cutaneous tissues repair are unclear.

Methods: We employed a self-controlled model (Sprague-Dawley rats with full-thickness skin wounds) to observe the action and effect of Wnt/β-catenin and Notch signalings in vivo. The quality of wound repair relevant to the gain/loss-of-function Wnt/β-catenin and Notch activation was estimated by hematoxylin-and-eosin and Masson staining. Immunofluorescence analysis and Western blot analysis were used to elucidate the underlying mechanism of the regulation of Wnt and Notch signaling pathways in wound healing. Meanwhile, epidermal stem cells (ESCs) were cultured in keratinocyte serum-free medium with Jaggedl or in DAPT (N-[(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl) to investigate whether the interruption of Notch signaling contributes to the expression of Wnt/β-catenin signaling.

Results: The results showed that in vivo the gain-of-function Wnt/β-catenin and Notch activation extended the ability to promote wound closure. We further determined that activation or inhibition of Wnt signaling and Notch signaling can affect the proliferation of ESCs, the differentiation and migration of keratinocytes, and follicle regeneration by targeting c-Myc and Hes1, which ultimately lead to enhanced or delayed wound healing. Furthermore, Western blot analysis suggested that the two pathways might interact in vivo and in vitro.

Conclusion: These results suggest that Wnt and Notch signalings play important roles in cutaneous repair by targeting c-Myc and Hes1 separately. What's more, interaction between the above two pathways might act as a vital role in regulation of wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Calcium-Binding Proteins / pharmacology
  • Cells, Cultured
  • Epidermal Cells
  • Female
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Male
  • Membrane Proteins / pharmacology
  • Microscopy, Fluorescence
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Notch / chemistry
  • Receptors, Notch / metabolism*
  • Serrate-Jagged Proteins
  • Signal Transduction / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Skin Diseases / therapy
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factor HES-1
  • Wnt Proteins / metabolism*
  • Wound Healing / physiology*
  • beta Catenin / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Hes1 protein, rat
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-myc
  • Receptors, Notch
  • Serrate-Jagged Proteins
  • Transcription Factor HES-1
  • Wnt Proteins
  • beta Catenin