Dataset Information

Enhanced Skin Incisional Wound Healing With Intracellular ATP Delivery via Macrophage Proliferation and Direct Collagen Production.

ABSTRACT: This study sought to use a newly developed intracellular ATP delivery to enhance incisional wound healing to reduce surgical wound dehiscence and to explore possible mechanism for this effect. Thirty-five adult New Zealand white rabbits were used. Skin incisions were made on the back and closed. ATP-vesicles were mixed with a neutral cream for one side of the wounds while the neutral cream alone was used on the other side of the wounds. Laser speckle contrast imaging (LSCI), biomechanical, histological, and immunohistochemical analyses were performed 7 and 14 days after surgery, and macrophage culture was used to test the enhanced collagen production ability. Among them, 10 were used for wound perfusion study and 25 were used for wound biomechanical and histological/immunohistochemical studies. Wound tissue perfusion was reduced after surgery especially in early days. Wound tissue tensile strength, breaking stress, and elasticity were all much higher in the ATP-vesicle treated group than in the cream treated group at days 7 and 14. The healing was complemented by earlier macrophage accumulation, in situ proliferation, followed by direct collagen production. The results were further confirmed by human macrophage culture. It was concluded that intracellular ATP delivery enhanced healing strength of incisional wounds via multiple mechanisms.

SUBMITTER: Sarojini H

PROVIDER: S-EPMC8241909 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Enhanced Skin Incisional Wound Healing With Intracellular ATP Delivery <i>via</i> Macrophage Proliferation and Direct Collagen Production.

Sarojini Harshini H Bajorek Alexander A Wan Rong R Wang Jianpu J Zhang Qunwei Q Billeter Adrian T AT Chien Sufan S

Frontiers in pharmacology 20210616

This study sought to use a newly developed intracellular ATP delivery to enhance incisional wound healing to reduce surgical wound dehiscence and to explore possible mechanism for this effect. Thirty-five adult New Zealand white rabbits were used. Skin incisions were made on the back and closed. ATP-vesicles were mixed with a neutral cream for one side of the wounds while the neutral cream alone was used on the other side of the wounds. Laser speckle contrast imaging (LSCI), biomechanical, histo ...[more]

PMID: 34220491

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Project description:This study investigates the effects of environmentally-relevant concentrations of fluoxetine (FLX, commercial name: Prozac) on wound healing. Pollution of water systems with pharmaceutical and care products, including antidepressants such as FLX and other selective serotonin reuptake inhibitors, is a growing environmental concern. Environmentally-relevant FLX concentrations are known to impact physiological functions and behaviour of aquatic animals, however, the effects of exposure on humans are currently unknown. Using a combination of human skin biopsies and keratinocyte cell lines, we show that exposure to environmental FLX enhances wound closure. We show dose-dependent increases in wound closure with FLX concentrations from 125 ng/l. We demonstrate that the mechanisms underlying enhanced wound closure are increased cell proliferation and serotonin signalling. Transcriptomic analysis revealed 350 differentially expressed genes after exposure. Downregulated genes were enriched in pathways related to mitochondrial function and metabolism, while upregulated genes were associated with cell proliferation and tissue morphogenesis. Kinase profiling showed altered phosphorylation of kinases related to the MAPK pathway. Consistent with this, phosphoproteomics analyses identified 235 differentially phosphorylated proteins after exposure, with enriched GO terms related to cell cycle, division, and protein biosynthesis. These findings collectively show that exposure to environmental FLX promotes wound healing through modulation of serotonin signalling, gene expression and protein phosphorylation, leading to enhanced cell proliferation. Our results open the door for further research to investigate the effects of environmental FLX on cell metabolism and proliferation, and clinical applications of FLX in the setting of wound healing. We argue that there is an urgent need to develop models that can inform on the risks, and potential benefits, of environmental pollution with selective serotonin reuptake inhibitors.

Dataset Information

Enhanced Skin Incisional Wound Healing With Intracellular ATP Delivery via Macrophage Proliferation and Direct Collagen Production.

Publications

Enhanced Skin Incisional Wound Healing With Intracellular ATP Delivery <i>via</i> Macrophage Proliferation and Direct Collagen Production.

Similar Datasets

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