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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Guo|Jian-Rong|JR|', 'Yin|Lei|L|', 'Chen|Yong-Quan|YQ|', 'Jin|Xiao-Ju|XJ|', 'Zhou|Xun|X|', 'Zhu|Na-Na|NN|', 'Liu|Xiao-Qian|XQ|', 'Wei|Han-Wei|HW|', 'Duan|Li-Shuang|LS|']
D000818:Animals D001804:Blood Transfusion, Autologous D003921:Diabetes Mellitus, Experimental D000071221:Enhancer of Zeste Homolog 2 Protein D044127:Epigenesis, Genetic D005347:Fibroblasts D005786:Gene Expression Regulation D006657:Histones D051795:Hypoxia-Inducible Factor 1, alpha Subunit D008297:Male D008745:Methylation D051379:Mice D062085:RNA, Long Noncoding D015398:Signal Transduction D014945:Wound Healing
Wound healing HIF-1α signaling pathway EZH2 Fibroblast activation Histone methylation Diabetes mellitus mice Long non-coding RNA H19 Modified autologous blood