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

Yan Shi, Bin Shu, Ronghua Yang, Yingbin Xu, Bangrong Xing, Jian Liu, Lei Chen, Shaohai Qi, Xusheng Liu, Peng Wang, Jinming Tang, Julin Xie

Wnt and Notch signaling pathways are critically involved in relative cell fate decisions within development of cutaneous tissues. Moreover, several studies identified the above two pathways as a significant role during wound healing. However, the biological effects of them are unclearly known during cutaneous tissues repair. 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 (H&E) 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, ESCs were cultured in keratinocyte serum-free medium (K-SFM) with Jaggedl, or DAPT to investigate whether the interruption of Notch signaling contributes to the expression of Wnt/β-catenin signaling. 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 follicles regeneration by targeting c-Myc and Hes1, which ultimately lead to enhanced or delayed wound healing. Furthermore, western blot analysis suggested that the two pathway might interact in vivo and in vitro. These results suggest that Wnt and Notch signalings play important roles in cutaneous repair by targeting c-Myc and Hes1, and indicate that interaction between the above two pathways might act as a subject investigated in regulation of action of the two pathways for treatment of wounds.