Cell Death Discovery (Apr 2022)

LncRNA XIST accelerates burn wound healing by promoting M2 macrophage polarization through targeting IL-33 via miR-19b

  • Li Pi,
  • Bairong Fang,
  • Xianxi Meng,
  • Li Qian

DOI
https://doi.org/10.1038/s41420-022-00990-x
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 10

Abstract

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Abstract 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.