microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells
microRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells
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microRNA-203 通过抑制表皮干细胞中的 Hes1 表达来调节伤口愈合和疤痕形成
DOI：
10.1159/000493834
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Xie, Julin
中科院分区：
文献类型：
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作者：
Zhou, Ziheng;Shu, Bin;Xie, Julin
背景/目的：miR-203如何参与表皮干细胞（ESCs）分化和疤痕形成尚不清楚。方法：我们首先采用荧光素酶法测定miR-203与3′-UTR在调控Hes1表达中的相互作用。然后我们使用流式细胞术通过测定CK15比率和α - sma来分析miR-203表达对ESCs向MFB分化的影响。为了证实流式细胞术分析的结果，我们使用Western blot检测pre-miR-203或anti-miR-203处理后ESCs中α - sma、胶原I （Col I）和胶原III （Col III）的表达以及Notch1、Jagged1和Hes1的表达。最后，我们通过小鼠皮肤伤口模型检测了局部抗mir -203治疗对伤口闭合和疤痕形成的影响。结果：通过降低CK15比率和增加MFB生物标志物，Pre-miR-203处理增加了ESCs向MFB细胞的分化。Hes1在ESCs中的过表达逆转了这一现象。此外，皮肤切口增加了创面组织中miR-203的表达。局部处理anti-miR-203可以加速伤口愈合，减少体内疤痕形成，这与再上皮化、皮肤附着再生和胶原蛋白再分配增加有关。最后，我们证实了anti-miR-203处理可以通过增加Hesl表达来抑制ESCs在体内的分化。结论：综上所述，我们的研究结果表明，皮肤创伤后ESCs中miR-203的过表达可能是瘢痕形成的关键机制。(C) 2018作者：s . Karger AG，巴塞尔出版
Background/Aims: Little is known how miR-203 is involved in epidermal stem cells (ESCs) differentiation and scar formation. Methods: We first used luciferase assay to determine the interaction of miR-203 with the 3'-UTR in regulation of Hes1 expression. We then used flow cytometry to analyze the effects of miR-203 expression on the differentiation of ESCs to MFB by determination of CK15 ratio and alpha-SMA. To confirm the results of flow cytometry analysis, we used Western blot to examine the expression of alpha-SMA, Collagen I (Col I), and Collagen III (Col III), as well as the expression of Notch1, Jagged1, and Hes1 in ESCs after the treatment of pre-miR-203 or anti-miR-203. Finally, we examined the effects local anti-miR-203 treatment on would closure and scar formation using a mouse skin wound model. Results: Pre-miR-203 treatment increased ESCs differentiation to MFB cells, as indicated by decreased CK15 ratio and increased MFB biomarkers. This phenomenon was reversed by overexpression of Hes1 in ESCs. In addition, skin incision increased expression of miR-203 in wound tissue. Local treatment of anti-miR-203 could accelerate wound closure and reduce scar formation in vivo, which was associated with increased re-epithelialization, skin attachment regeneration, and collagen reassignment. Finally, we confirmed that anti-miR-203 treatment could inhibit ESCs differentiation in vivo via increasing Hesl expression. Conclusion: Taken together, our results suggested that overexpression of miR-203 in ESCs after skin wound may be a critical mechanism underlying the scar formation. (C) 2018 The Author(s) Published by S. Karger AG, Basel