Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately.
Wnt and Notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately.
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Wnt和Notch信号通路分别通过靶向c-Myc和Hes1参与伤口愈合。
DOI：
10.1186/s13287-015-0103-4
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发表时间：
2015-06-16
影响因子：
7.5
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Shi Y;Shu B;Yang R;Xu Y;Xing B;Liu J;Chen L;Qi S;Liu X;Wang P;Tang J;Xie J
Wnt和Notch信号通路在皮肤组织发育中的相对细胞命运决定中起关键作用。此外，一些研究确定上述两种途径在伤口愈合过程中具有重要作用。然而，它们在皮肤组织修复过程中的生物学效应尚不清楚。我们采用自身对照模型（Sprague-Dawley大鼠全层皮肤创伤）观察Wnt/β-catenin和Notch信号通路在体内的作用和影响。通过苏木精-伊红和Masson染色评估与功能获得/丧失Wnt/β-catenin和Notch活化相关的伤口修复质量。免疫荧光分析和Western blot分析用于阐明Wnt和Notch信号通路在伤口愈合中的调节的潜在机制。同时，将表皮干细胞（ESC）培养在含有Jaggedl的角质形成细胞无血清培养基或DAPT（N-[（3，5-二氟苯基）乙酰基]-L-丙氨酰-2-苯基]甘氨酸-1，1-二甲基乙基）中，以研究Notch信号传导的中断是否有助于Wnt/β-连环蛋白信号传导的表达。结果表明，在体内，功能获得性Wnt/β-catenin和Notch激活延长了促进伤口闭合的能力。我们进一步确定Wnt信号传导和Notch信号传导的激活或抑制可以通过靶向c-Myc和Hes 1影响ESC的增殖、角质形成细胞的分化和迁移以及卵泡再生，最终导致伤口愈合的增强或延迟。Western blot分析表明，这两条通路在体内和体外可能存在相互作用。这些结果表明，Wnt和Notch信号通过分别靶向c-Myc和Hes 1在皮肤修复中发挥重要作用。此外，上述两条通路之间的相互作用可能在伤口愈合的调节中起着重要作用。
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. 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. 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. 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.