Chen Xiao-Dong, Ruan Shu-Bin, Lin Ze-Peng, Zhou Ziheng, Zhang Feng-Gang, Yang Rong-Hua, Xie Ju-Lin
a Department of Burn Surgery , The First People's Hospital of Foshan , Foshan , Guangdong , China.
b Department of Burn Surgery , First Affiliated Hospital of Sun Yat-Sen University , Guangzhou , Guangdong , China.
Organogenesis. 2018 Jan 2;14(1):25-35. doi: 10.1080/15476278.2018.1436023. Epub 2018 Apr 27.
Skin wound healing involves Notch/Jagged1 signaling. However, little is known how Jag1 expression level in epidermal stem cells (ESCs) contributes to wound healing and scar formation. We applied multiple cellular and molecular techniques to examine how Jag1 expression in ESCs modulates ESCs differentiation to myofibroblasts (MFB) in vitro, interpret how Jag1 expression in ESCs is involved in wound healing and scar formation in mice, and evaluate the effects of porcine acellular dermal matrix (ADM) treatment on wound healing and scar formation. We found that Jag1, Notch1 and Hes1 expression was up-regulated in the wound tissue during the period of wound healing. Furthermore, Jag1 expression level in the ESCs was positively associated with the level of differentiation to MFB. ESC-specific knockout of Jag1 delayed wound healing and promoted scar formation in vivo. In addition, we reported that porcine ADM treatment after skin incision could accelerate wound closure and reduce scar formation in vivo. This effect was associated with decreased expression of MFB markers, including α-SMA Col-1 and Col-III in wound tissues. Finally, we confirmed that porcine ADM treatment could increase Jag1, Notch1 and Hesl expression in wound tissues. Taken together, our results suggested that ESC-specific Jag1 expression levels are critical for wound healing and scar formation, and porcine ADM treatment would be beneficial in promoting wound healing and preventing scar formation by enhancing Notch/Jagged1 signaling pathway in ESCs.
皮肤伤口愈合涉及Notch/Jagged1信号通路。然而，对于表皮干细胞（ESC）中Jag1表达水平如何影响伤口愈合和瘢痕形成知之甚少。我们应用多种细胞和分子技术来研究ESC中Jag1的表达如何在体外调节ESC向肌成纤维细胞（MFB）的分化，解释ESC中Jag1的表达如何参与小鼠的伤口愈合和瘢痕形成，并评估猪脱细胞真皮基质（ADM）处理对伤口愈合和瘢痕形成的影响。我们发现，在伤口愈合期间，伤口组织中Jag1、Notch1和Hes1的表达上调。此外，ESC中Jag1的表达水平与向MFB的分化水平呈正相关。ESC特异性敲除Jag1会延迟体内伤口愈合并促进瘢痕形成。此外，我们报道皮肤切开后进行猪ADM处理可加速体内伤口闭合并减少瘢痕形成。这种作用与伤口组织中包括α-SMA、Col-1和Col-III在内 的MFB标志物表达降低有关。最后，我们证实猪ADM处理可增加伤口组织中Jag1、Notch1和Hes1的表达。综上所述，我们的结果表明，ESC特异性Jag1表达水平对伤口愈合和瘢痕形成至关重要，猪ADM处理通过增强ESC中的Notch/Jagged1信号通路，对促进伤口愈合和预防瘢痕形成有益。
