title: Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. 408561894@qq.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. shubin29@sina.com
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.affiliation: Department of Burns, Fo Shan Hospital of Sun Yat-Sen University, Lingnan avenue, Foshan, 528000, China. 21720091@qq.com.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. 254911568@qq.com.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Burns, Third Affiliated Hospital of Sun Yat-sen University, Tianhe road, Guangzhou, 510620, China. 1030791795@qq.com.
authors.forename: Bangrong
authors.initials: B
authors.lastname: Xing
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. 542588725@qq.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. foodshiyan@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. 962093595@qq.com.
authors.forename: Shaohai
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. 79951927@qq.com.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. 1011427849@qq.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. tangjinm@mail.sysu.edu.cn.
authors.forename: Jinming
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Burns Surgery, First Affiliated Hospital of Sun Yat-Sen University, Zhongshan road, Guangzhou, 510080, China. xiejl90@sina.com.
authors.forename: Julin
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D005260:Female; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000737:chemistry / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000628:therapy; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D000072056:Transcription Factor HES-1; D051153:Wnt Proteins / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; D051153:Wnt Proteins; D051176:beta Catenin; C489735:Hes1 protein, rat