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Novel 14S,21-dihydroxy-docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure.

ABSTRACT: Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here, we found that AE diminished the formation of novel reparative lipid mediator 14S,21-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21-diHDHA) and its biosynthetic intermediate 14S-hydroxy-DHA (14S-HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21-HDHA. These results indicate that in the biosynthetic pathways of 14S,21-diHDHA in wounds, AE suppresses the 14S-hydroxy-generating activity of 12-lipoxygenase-like (LOX-like), but does not suppress the 21-hydroxy-generating activity of cytochrome P450 and DHA-generating activities. The AE-suppression of 12-LOX-like activity was further confirmed by the diminished formation of 12-hydroxy-eicosatetraenoic acid in wounds under AE. Supplementing 14S,21-diHDHA to wounds rescued the AE-impaired healing and vascularization. 14S,21-diHDHA restored AE-impaired processes of angiogenesis in vitro: endothelial cell migration, tubulogenesis, and phosphorylation of p38 mitogen-activated protein kinase (MAPK). Taken together, the suppression of 14S,21-diHDHA formation is responsible, at least partially, for the AE-impairment of cutaneous wound healing and angiogenesis. Supplementing 14S,21-diHDHA to compensate its deficit in AE-impaired wounds rescues the healing and angiogenesis. These results provide a novel mechanistic insight for AE-impaired wound healing that involves the necessary roles of 14S,21-diHDHA. They also offer leads for developing 14S,21-diHDHA-related therapeutics to ameliorate AE-impairment of wound healing.

SUBMITTER: Tian H

PROVIDER: S-EPMC3308707 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Novel 14S,21-dihydroxy-docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure.

Tian Haibin H Lu Yan Y Shah Shraddha P SP Hong Song S

Journal of cellular biochemistry 20101001 2

Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here, we found that AE diminished the formation of novel reparative lipid mediator 14S,21-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21-diHDHA) and its biosynthetic intermediate 14S-hydroxy-DHA (14S-HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21-HDHA. These results indicate that in the bio ...[more]

PMID: 20506249

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Project description:The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This study aimed to investigate the effects of exosomes from human umbilical cord blood plasma (UCB-Exos) on wound healing and to elucidate the underlying mechanism. Methods: UCB-Exos were isolated by ultracentrifugation and subcutaneously injected into full-thickness skin wounds in mice. The efficacy of UCB-Exos on wound healing was evaluated by measuring wound closure rates, histological analysis and immunofluorescence examinations. In vitro, quantitative real-time PCR (qRT-PCR) analysis was performed to detect the expression levels of a class of miRNAs that have positive roles in regulating wound healing. The scratch wound assay, transwell assay and cell counting kit-8 analysis were conducted to assess the effects of UCB-Exos on migration and proliferation of human skin fibroblasts and endothelial cells. Tube formation assay was carried out to test the impact of UCB-Exos on angiogenic tube formation ability of endothelial cells. Meanwhile, by using specific RNA inhibitors or siRNAs, the roles of the candidate miRNA and its target genes in UCB-Exos-induced regulation of function of fibroblasts and endothelial cells were assessed. Results: The local transplantation of UCB-Exos into mouse skin wounds resulted in accelerated re-epithelialization, reduced scar widths, and enhanced angiogenesis. In vitro, UCB-Exos could promote the proliferation and migration of fibroblasts, and enhance the angiogenic activities of endothelial cells. Notably, miR-21-3p was found to be highly enriched in UCB-Exos and served as a critical mediator in UCB-Exos -induced regulatory effects through inhibition of phosphatase and tensin homolog (PTEN) and sprouty homolog 1 (SPRY1). Conclusion: Our results suggest that UCB-Exos are important effectors of plasma activity and can be used as a novel promising strategy for soft tissue wound healing.

Dataset Information

Novel 14S,21-dihydroxy-docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure.

Publications

Novel 14S,21-dihydroxy-docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure.

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