PMID- 30458806 OWN - NLM STAT- MEDLINE DCOM- 20190515 LR - 20190515 IS - 1478-811X (Electronic) IS - 1478-811X (Linking) VI - 16 IP - 1 DP - 2018 Nov 20 TI - Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1alpha signaling pathway. PG - 84 LID - 10.1186/s12964-018-0290-6 [doi] LID - 84 AB - 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-1alpha. 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-1alpha histone H3K4me3 methylation and increased HIF-1alpha expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1alpha 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-1alpha signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice. FAU - Guo, Jian-Rong AU - Guo JR AD - Department of Anesthesiology, Gongli Hospital, the Second Military Medical University, No. 219, Miaopu Road, Pudong New Area, Shanghai, 200135, People's Republic of China. g_jianrong@126.com. AD - Ningxia Medical University, Gongli Hospital of Shanghai Pudong New Area Training Base, Shanghai, 200135, People's Republic of China. g_jianrong@126.com. FAU - Yin, Lei AU - Yin L AD - Department of Anesthesiology, Yijishan Hospital, the Wannan Medical College, Wuhu, 241001, People's Republic of China. FAU - Chen, Yong-Quan AU - Chen YQ AD - Department of Anesthesiology, Yijishan Hospital, the Wannan Medical College, Wuhu, 241001, People's Republic of China. FAU - Jin, Xiao-Ju AU - Jin XJ AD - Department of Anesthesiology, Yijishan Hospital, the Wannan Medical College, Wuhu, 241001, People's Republic of China. FAU - Zhou, Xun AU - Zhou X AD - Department of Anesthesiology, Gongli Hospital, the Second Military Medical University, No. 219, Miaopu Road, Pudong New Area, Shanghai, 200135, People's Republic of China. FAU - Zhu, Na-Na AU - Zhu NN AD - Department of Anesthesiology, Gongli Hospital, the Second Military Medical University, No. 219, Miaopu Road, Pudong New Area, Shanghai, 200135, People's Republic of China. FAU - Liu, Xiao-Qian AU - Liu XQ AD - Department of Anesthesiology, Gongli Hospital, the Second Military Medical University, No. 219, Miaopu Road, Pudong New Area, Shanghai, 200135, People's Republic of China. FAU - Wei, Han-Wei AU - Wei HW AD - Department of Anesthesiology, Gongli Hospital, the Second Military Medical University, No. 219, Miaopu Road, Pudong New Area, Shanghai, 200135, People's Republic of China. FAU - Duan, Li-Shuang AU - Duan LS AD - Department of Anesthesiology, Gongli Hospital, the Second Military Medical University, No. 219, Miaopu Road, Pudong New Area, Shanghai, 200135, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181120 PL - England TA - Cell Commun Signal JT - Cell communication and signaling : CCS JID - 101170464 RN - 0 (H19 long non-coding RNA) RN - 0 (Histones) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (RNA, Long Noncoding) RN - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) RN - EC 2.1.1.43 (Ezh2 protein, mouse) SB - IM MH - Animals MH - *Blood Transfusion, Autologous MH - Diabetes Mellitus, Experimental/genetics/metabolism/pathology/*therapy MH - Enhancer of Zeste Homolog 2 Protein/metabolism MH - Epigenesis, Genetic MH - Fibroblasts/metabolism MH - *Gene Expression Regulation MH - Histones/metabolism MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Male MH - Methylation MH - Mice MH - RNA, Long Noncoding/*genetics MH - Signal Transduction/*genetics MH - Wound Healing/*genetics PMC - PMC6245761 OTO - NOTNLM OT - Diabetes mellitus mice OT - EZH2 OT - Fibroblast activation OT - HIF-1alpha signaling pathway OT - Histone methylation OT - Long non-coding RNA H19 OT - Modified autologous blood OT - Wound healing COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study was conducted under the approval of the Ethics Committee of Gongli Hospital, the Second Military Medical University. All animal experiments in this study conformed to the principles of the management and use of local experimental animals and followed the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that there are no competing interests associated with the manuscript. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/11/22 06:00 MHDA- 2019/05/16 06:00 PMCR- 2018/11/20 CRDT- 2018/11/22 06:00 PHST- 2018/07/25 00:00 [received] PHST- 2018/10/25 00:00 [accepted] PHST- 2018/11/22 06:00 [entrez] PHST- 2018/11/22 06:00 [pubmed] PHST- 2019/05/16 06:00 [medline] PHST- 2018/11/20 00:00 [pmc-release] AID - 10.1186/s12964-018-0290-6 [pii] AID - 290 [pii] AID - 10.1186/s12964-018-0290-6 [doi] PST - epublish SO - Cell Commun Signal. 2018 Nov 20;16(1):84. doi: 10.1186/s12964-018-0290-6.