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

Abstract

IntroductionWnt 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.MethodsWe 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.ResultsThe 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.ConclusionThese 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.

Notch/Wnt cross-signalling regulates stemness of dental pulp stem cells through expression of neural crest and core pluripotency factors

“…In view of this evidence, the question became what connection do these pathways have at the molecular level? Many positive and negative interactions are reported between both pathways in a myriad of model systems (Borggrefe et al, 2016;Fukunaga-Kalabis et al, 2015;Kwon et al, 2011;Nicolas et al, 2003;Shi et al, 2015). In colorectal cancer cells, Wnt signalling affects Notch through β-catenin-mediated transcriptional activation of the gene Jagged1 (Rodilla et al, 2009).…”

Scarless wound healing: finding the right cells and signals

“…It thus follows that overexpression of endogenous Dkk-1 in a transgenic mouse line prevented bleomycin-induced fibrosis. (Akhmetshina, et al, 2012) However, topical application of Dkk-1 in a full-thickness excisional model inhibited wound healing (Shi, et al, 2015). Therefore, harnessing Dkk-1 for therapeutic intervention will require further insight into its mechanism of action, particularly as it relates to fibrotic etiology and means of administration.…”

“…Wnt activation with lithium chloride (LiCl) in turn reduced regenerative repair. (Bastakoty, et al, 2015) However, in a full thickness excisional wound model in rats, topical LiCl application demonstrated reduction in gross scar appearance without impacting time to wound closure (Shi, et al, 2015). As in the case with therapeutic Dkk-1 administration, more studies are needed to produce the desired regenerative healing phenotype in vivo .…”

microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

“…Digital planimetry was used to measure wound area with ImageJ software version 2.1.4.6 (NIH, Bethesda, MD). The wound residual rate and scar index were calculated using the formula as described previously [32]. Quantitative real-time PCR Total RNA was extracted from the wound tissue samples using Trizol Reagent (Invitrogen, Shanghai, China), and then transcribed into cDNA using the PrimeScript RT reagent Kit (Takara, Shanghai, China).…”