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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

Cell communication and signaling : CCS - 16(2018), 1 vom: 20. Nov., Seite 84

Sprache:

Englisch

Beteiligte Personen:

Guo, Jian-Rong [VerfasserIn]
Yin, Lei [VerfasserIn]
Chen, Yong-Quan [VerfasserIn]
Jin, Xiao-Ju [VerfasserIn]
Zhou, Xun [VerfasserIn]
Zhu, Na-Na [VerfasserIn]
Liu, Xiao-Qian [VerfasserIn]
Wei, Han-Wei [VerfasserIn]
Duan, Li-Shuang [VerfasserIn]

Links:

Volltext

Themen:

Diabetes mellitus mice
EC 2.1.1.43
EZH2
Enhancer of Zeste Homolog 2 Protein
Ezh2 protein, mouse
Fibroblast activation
H19 long non-coding RNA
HIF-1α signaling pathway
Histone methylation
Histones
Hypoxia-Inducible Factor 1, alpha Subunit
Journal Article
Long non-coding RNA H19
Modified autologous blood
RNA, Long Noncoding
Research Support, Non-U.S. Gov't
Wound healing

Anmerkungen:

Date Completed 15.05.2019

Date Revised 15.05.2019

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s12964-018-0290-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM290904048