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小窝蛋白-1在大鼠烧伤创面愈合过程中对表皮干细胞的作用

Role of caveolin-1 in epidermal stem cells during burn wound healing in rats.

作者信息

Yang Ronghua, Wang Jingru, Zhou Ziheng, Qi Shaohai, Ruan Shubin, Lin Zepeng, Xin Qi, Lin Yan, Chen Xiaodong, Xie Julin

机构信息

Department of Burn Surgery, the First People's Hospital of Foshan, Foshan 528000, Guangdong, China.

Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, Guangdong, China.

出版信息

Dev Biol. 2019 Jan 15;445(2):271-279. doi: 10.1016/j.ydbio.2018.11.015. Epub 2018 Nov 23.

Abstract

Local transplantation of stem cells has therapeutic effects on skin damage but cannot provide satisfactory wound healing. Studies on the mechanisms underlying the therapeutic effects of stem cells on skin wound healing will be needed. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. We first isolated EpiSCs from mouse skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct. We then evaluated the epidermal growth factor (EGF)-induced cell proliferation ability using cell counting Kit-8 (CCK-8) assay and assessed EpiSC pluripotency by examining Nanog mRNA levels in EpiSCs. Furthermore, we treated mice with skin burn injury using EpiSCs with overexpression of Caveolin-1. Histological examinations were conducted to evaluate re-epithelialization, wound scores, cell proliferation and capillary density in wounds. We found that overexpression of Caveolin-1 in EpiSCs promoted EGF-induced cell proliferation ability and increased wound closure in a mouse model of skin burn injury. Histological evaluation demonstrated that overexpression of Caveolin-1 in EpiSCs promoted re-epithelialization in wounds, enhanced cellularity, and increased vasculature, as well as increased wound scores. Taken together, our results suggested that Caveolin-1 expression in the EpiSCs play a critical role in the regulation of EpiSC proliferation ability and alteration of EpiSC proliferation ability may be an effective approach in promoting EpiSC-based therapy in skin wound healing.

摘要

干细胞的局部移植对皮肤损伤具有治疗作用,但无法实现令人满意的伤口愈合。因此,有必要对干细胞促进皮肤伤口愈合的治疗作用机制展开研究。故而,在本研究中,我们探究了小窝蛋白-1在表皮干细胞(EpiSCs)调节伤口愈合过程中的作用。我们首先从小鼠皮肤组织中分离出EpiSCs,并使用慢病毒构建体建立了稳定过表达小窝蛋白-1的EpiSCs。然后,我们使用细胞计数试剂盒-8(CCK-8)检测评估表皮生长因子(EGF)诱导的细胞增殖能力,并通过检测EpiSCs中Nanog mRNA水平来评估EpiSC的多能性。此外,我们用过量表达小窝蛋白-1的EpiSCs治疗皮肤烧伤的小鼠。进行组织学检查以评估伤口的再上皮化、伤口评分、细胞增殖和毛细血管密度。我们发现,EpiSCs中过表达小窝蛋白-1可促进EGF诱导的细胞增殖能力,并增加皮肤烧伤小鼠模型中的伤口闭合。组织学评估表明,EpiSCs中过表达小窝蛋白-1可促进伤口的再上皮化,增强细胞数量,增加血管生成,同时提高伤口评分。综上所述,我们的结果表明,EpiSCs中的小窝蛋白-1表达在调节EpiSC增殖能力中起关键作用,改变EpiSC增殖能力可能是促进基于EpiSC的皮肤伤口愈合治疗的有效方法。

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