Preservation of denatured dermis exerts promotive functions in wound healing and improves the appearance and function of skin. Angiogenesis is crucial for wound healing during burn injury. However, the potential molecular mechanism of angiogenesis in the recovery after burn injury remains to be elucidated. Herein, RNA chromatin immunoprecipitation (ChIP) sequencing analysis revealed upregulation of long intergenic non-coding RNA 00174 (linc00174) in the post-burn tissues. linc00174 overexpression promoted angiogenic activities of human umbilical vein endothelial cells (HUVECs) in the heat-denatured cell model, characterized by the promotion of cell proliferation, migration, and tube formation. Mechanistically, linc00174 directly bound to enhancer of zeste homolog 2 (EZH2), thus stimulating the protein level of trimethylation at lysine 27 of histone H3 (H3K27me3). Moreover, inhibition of EZH2 resulted in downregulation of ZNF24 and Runx1, as well as a decline of vascular endothelial growth factor A (VEGFA). Furthermore, EZH2 modulated epigenetic repression of ZNF24 and Runx1 through the promoter of H3K27me3. Additionally, ZNF24 and Runx1 both functioned as transcriptional inhibitors of VEGFA. Taken together, these findings uncover that linc00174 epigenetically inhibits ZNF24 and Runx1 expression through binding to EZH2, thus attenuating the suppression of VEGFA, contributing to the facilitation of angiogenesis during the recovery of heat-denatured endothelial cells.

保存变性的真皮在伤口愈合中起到促进作用，并改善皮肤的外观和功能。血管生成对于烧伤过程中的伤口愈合至关重要。然而，烧伤后恢复中血管新生的潜在分子机制仍有待阐明。在本文中，RNA染色质免疫沉淀（ChIP）测序分析揭示了烧伤后组织中长基因间非编码RNA 00174（linc00174）的上调。linc00174在热变性细胞模型中，过表达促进人脐静脉内皮细胞（HUVEC）的血管生成活性，其特征在于促进细胞增殖，迁移和管形成。机械上，linc00174直接与zeste同系物2（EZH2）的增强子结合，因此刺激了组蛋白H3（H3K27me3）的赖氨酸27处的三甲基化蛋白水平。此外，对EZH2的抑制导致ZNF24和Runx1的下调，以及血管内皮生长因子A（VEGFA）的下降。此外，EZH2通过H3K27me3的启动子调节ZNF24和Runx1的表观遗传抑制。此外，ZNF24和Runx1均作为VEGFA的转录抑制剂。综上所述，这些发现揭示了linc00174通过与EZH2结合而表观遗传地抑制ZNF24和Runx1的表达，从而减弱了对VEGFA的抑制，在热变性内皮细胞的恢复过程中促进了血管生成。以及血管内皮生长因子A（VEGFA）的下降。此外，EZH2通过H3K27me3的启动子调节ZNF24和Runx1的表观遗传抑制。此外，ZNF24和Runx1均作为VEGFA的转录抑制剂。综上所述，这些发现揭示了linc00174通过与EZH2结合而表观遗传地抑制ZNF24和Runx1的表达，从而减弱了对VEGFA的抑制，在热变性内皮细胞的恢复过程中促进了血管生成。以及血管内皮生长因子A（VEGFA）的下降。此外，EZH2通过H3K27me3的启动子调节ZNF24和Runx1的表观遗传抑制。此外，ZNF24和Runx1均作为VEGFA的转录抑制剂。综上所述，这些发现揭示了linc00174通过与EZH2结合而表观遗传地抑制ZNF24和Runx1的表达，从而减弱了对VEGFA的抑制，在热变性内皮细胞恢复过程中促进了血管生成。