Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway

• Published in: Cell communication and signaling 2018-11, Vol.16 (1), p.84-84, Article 84
• Main Authors: Guo, Jian-Rong, Yin, Lei, Chen, Yong-Quan, Jin, Xiao-Ju, Zhou, Xun, Zhu, Na-Na, Liu, Xiao-Qian, Wei, Han-Wei, Duan, Li-Shuang
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Blood; Blood transfusion; Blood Transfusion, Autologous; Blood transfusions; Breast cancer; Cell growth; Chromatin; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - therapy; Enhancer of Zeste Homolog 2 Protein - metabolism; Epigenesis, Genetic; EZH2; Fibroblast activation; Fibroblasts; Fibroblasts - metabolism; Fluorescence in situ hybridization; Gene Expression Regulation; HIF-1α signaling pathway; Histone methylation; Histones - metabolism; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunoprecipitation; Inflammation; Laboratory animals; Long non-coding RNA H19; Male; Methylation; Mice; Modified autologous blood; Non-coding RNA; Oxygen; Reporter gene; RNA, Long Noncoding - genetics; Rodents; Signal transduction; Signal Transduction - genetics; Skin; Streptozocin; Surgery; Tissue engineering; Wound healing; Wound Healing - genetics
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-018-0290-6

Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid. Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α. The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice. Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice.