Effects of porcine acellular dermal matrix treatment on wound healing and scar formation: Role of Jag1 expression in epidermal stem cells
Effects of porcine acellular dermal matrix treatment on wound healing and scar formation: Role of Jag1 expression in epidermal stem cells
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猪脱细胞真皮基质治疗对伤口愈合和疤痕形成的影响：表皮干细胞中 Jag1 表达的作用
DOI：
10.1080/15476278.2018.1436023
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发表时间：
2018-01-01
期刊：
影响因子：
2.3
通讯作者：
Xie, Ju-Lin
中科院分区：
文献类型：
--
作者：
Chen, Xiao-Dong;Ruan, Shu-Bin;Xie, Ju-Lin
皮肤创伤愈合涉及Notch/Jagged 1信号转导。然而，很少有人知道Jag 1在表皮干细胞（ESCs）的表达水平如何有助于伤口愈合和瘢痕形成。我们应用多种细胞和分子技术来研究Jag 1在ESCs中的表达如何调节ESCs在体外向肌成纤维细胞（MFB）分化，解释Jag 1在ESCs中的表达如何参与小鼠伤口愈合和瘢痕形成，并评估猪脱细胞真皮基质（ADM）治疗对伤口愈合和瘢痕形成的影响。我们发现在创伤愈合过程中，Jag 1、Notch 1和Hes 1在创伤组织中表达上调。此外，Jag 1在ESCs中的表达水平与向MFB的分化水平呈正相关。ESC特异性敲除Jag 1可延迟伤口愈合并促进体内瘢痕形成。此外，我们报告了猪ADM治疗皮肤切口后，可以加速伤口愈合，减少瘢痕形成在体内。该效应与MFB标志物（包括伤口组织中的α-SMA Col-1和Col-III）的表达降低相关。最后，我们证实了猪ADM治疗可以增加伤口组织中Jag 1、Notch 1和Hesl的表达。综上所述，我们的研究结果表明，ESCs特异性Jag 1表达水平对伤口愈合和瘢痕形成至关重要，猪ADM治疗将有利于促进伤口愈合和预防瘢痕形成，通过增强ESCs中的Notch/Jagged 1信号通路。
ABSTRACT 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.