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长链非编码 RNA HOTAIR 通过调节表皮干细胞促进烧伤创面愈合。

Long non‑coding RNA HOTAIR promotes burn wound healing by regulating epidermal stem cells.

机构信息

Burns Institute, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Burns Department, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China.

出版信息

Mol Med Rep. 2020 Sep;22(3):1811-1820. doi: 10.3892/mmr.2020.11268. Epub 2020 Jun 23.

Abstract

Local transplantation of epidermal stem cells (ESCs) exerts a therapeutic effect on burn wounds. However, cell viability can impede their clinical application. HOX antisense intergenic RNA (HOTAIR) is involved in regulating adult tissue stem cells, as well as in developmental patterning and pluripotency. However, little is known about its role in regulating ESCs. The present study was performed to investigate the effects of HOTAIR in the modulation of ESCs and wound repair. Firstly, reverse transcription‑quantitative PCR was used to detect the relative expression of HOTAIR during burn wound healing in mice to determine whether HOTAIR is associated with wound healing. Subsequently, ESCs derived from mouse skin were transfected with a lentiviral vector to overexpress or knockdown HOTAIR. The effects of HOTAIR on cell proliferation and differentiation were measured by 5‑bromodeoxyuridine and MTT assays, and by assessing NANOG mRNA expression. Lastly, mice with burns were administered a subcutaneous injection of HOTAIR‑overexpressing ESCs. Images were captured and histological analyses were performed to evaluate wound healing. The results revealed that the expression of HOTAIR gradually increased and peaked at day 7 post‑burn and maintained at relatively high levels until day 14 post‑burn during wound healing. Furthermore, overexpression of HOTAIR promoted ESC proliferation and maintained the stem cell state in vitro. By contrast, suppression of HOTAIR inhibited cell proliferation and cell stemness. It was also identified that HOTIR‑overexpressing ESCs accelerated re‑epithelialization and facilitated burn wound repair. In conclusion, the present findings confirmed an essential role of HOTAIR in the regulation of ESC proliferation and stemness. Therefore, targeting HOTAIR in ESCs may be a potentially promising therapy for burn wound healing.

摘要

局部移植表皮干细胞(ESCs)对烧伤创面具有治疗作用。然而,细胞活力会阻碍其临床应用。HOX 反义基因间 RNA(HOTAIR)参与调节成体组织干细胞,以及发育模式和多能性。然而,其在调节 ESCs 中的作用知之甚少。本研究旨在探讨 HOTAIR 在调节 ESCs 和伤口修复中的作用。首先,采用逆转录-定量 PCR 检测小鼠烧伤创面愈合过程中 HOTAIR 的相对表达,以确定 HOTAIR 是否与创面愈合有关。随后,用慢病毒载体转染小鼠皮肤来源的 ESCs,过表达或敲低 HOTAIR。通过 5-溴脱氧尿苷和 MTT 检测,以及评估 NANOG mRNA 表达,检测 HOTAIR 对细胞增殖和分化的影响。最后,对烧伤小鼠进行 HOTAIR 过表达 ESCs 的皮下注射。拍摄图像并进行组织学分析,以评估伤口愈合。结果显示,HOTAIR 的表达在烧伤后逐渐增加,并在第 7 天达到峰值,在创面愈合过程中直至第 14 天仍维持在相对较高的水平。此外,过表达 HOTAIR 促进 ESC 增殖,并维持体外干细胞状态。相反,抑制 HOTAIR 抑制细胞增殖和细胞干性。还发现 HOTAIR 过表达 ESCs 加速上皮再形成并促进烧伤创面修复。综上所述,本研究结果证实了 HOTAIR 在调节 ESC 增殖和干性中的重要作用。因此,靶向 ESCs 中的 HOTAIR 可能是一种有前途的烧伤创面愈合治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0553/7411415/6d8263f6ed70/MMR-22-03-1811-g00.jpg

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