Pi Li, Fang Bairong, Meng Xianxi, Qian Li
The Department of Burn and Plastic Surgery, the Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Cell Death Discov. 2022 Apr 21;8(1):220. doi: 10.1038/s41420-022-00990-x.
Burn injuries are a serious threat to quality of life. The aim of this study was to investigate the mechanism of burn wound healing. The lncRNA XIST has been associated with burn wound healing, but the mechanism is not clear. In the present study, in vitro and in vivo models of burn injuries were established by thermal injury treatment of human skin fibroblasts (HSFs) and mice, respectively. Pathological changes in skin tissues were detected by haematoxylin and eosin (HE) staining. Immunofluorescence double staining was performed to detect M2 macrophages. Furthermore, the changes of cell proliferation, apoptosis and migration by CCK-8, flow cytometry, scratch and Transwell assays to evaluate the effect of XIST on burn wound healing. The binding relationships among XIST, miR-19b and IL-33 were analyzed by RNA immunoprecipitation (RIP) and dual luciferase reporter assays. Our results found that there were targeted binding sites between XIST and miR-19b, miR-19b and IL-33. We investigated whether XIST enhanced the polarization of M2 macrophages to promote the healing of burn wounds. After fibroblast burn injury, the expression levels of XIST and IL-33 increased in a time-dependent manner, whereas miR-19b expression decreased in a time-dependent manner. XIST contributed to the proliferation and migration of skin fibroblasts by inhibiting miR-19b and enhanced fibroblast extracellular matrix production by promoting the transformation of macrophages to the M2 phenotype. In short, these findings indicate that XIST can promote burn wound healing and enhance the polarization of M2 macrophages by targeting the IL-33/miR-19b axis, which may serve as a potential theoretical basis for the treatment of burn wound healing.
烧伤对生活质量构成严重威胁。本研究旨在探讨烧伤创面愈合的机制。长链非编码RNA XIST与烧伤创面愈合有关，但其机制尚不清楚。在本研究中，分别通过对人皮肤成纤维细胞（HSFs）和小鼠进行热损伤处理，建立了烧伤的体外和体内模型。通过苏木精和伊红（HE）染色检测皮肤组织的病理变化。进行免疫荧光双染色以检测M2巨噬细胞。此外，通过CCK-8、流式细胞术、划痕试验和Transwell试验检测细胞增殖、凋亡和迁移的变化，以评估XIST对烧伤创面愈合的影响。通过RNA免疫沉淀（RIP）和双荧光素酶报告基因试验分析XIST、miR-19b和IL-33之间的结合关系。我们的结果发现XIST与miR-19b、miR-19b与IL-33之间存在靶向结合位点。我们研究了XIST是否增强M2巨噬细胞的极化以促进烧伤创面的愈合。成纤维细胞烧伤损伤后，XIST和IL-33的表达水平呈时间依赖性增加，而miR-19b的表达呈时间依赖性降低。XIST通过抑制miR-19b促进皮肤成纤维细胞的增殖和迁移，并通过促进巨噬细胞向M2表型转化增强成纤维细胞外基质的产生。简而言之，这些发现表明XIST可通过靶向IL-33/miR-19b轴促进烧伤创面愈合并增强M2巨噬细胞的极化，这可能为烧伤创面愈合的治疗提供潜在的理论基础。
