{"title":"Activation of adenosine A2a and A2b receptors augments the skin wound healing in juvenile grass carp","authors":"","doi":"10.1016/j.aquaculture.2024.741674","DOIUrl":null,"url":null,"abstract":"<div><div>Wounded fish skin leads to the impairment of internal tissue homeostasis and provides an opportunity for pathogens to invade, resulting in the occurrence of fish diseases. Accordingly, skin wound healing has been investigated in many fishes. In the present study, we found that the concentration of adenosine increased in grass carp skin wounds and antagonization of adenosine receptors aggravated the skin wound closure, implying that adenosine receptor activation played a role in fish skin wound repair. After the expression of adenosine A<sub>2a</sub> receptor (A<sub>2a</sub>R) and A<sub>2b</sub>R in grass carp skin was verified, the effects of two adenosine analogs, ZM241385 and CGS 21680, on grass carp A<sub>2a</sub>R and A<sub>2b</sub>R activation were examined by a dual-luciferase assay. The results showed that 500 nM of ZM241385 could antagonize the activation of both receptors by adenosine and 5–5000 nM of CGS 21680 could stimulate both receptors. In this scenario, these two compounds were administrated to the skin wounds of juvenile grass carp weighting about 8.0 g each, showing that 0.5, 2.5, 12.5 μg/tail of ZM241385 dose-dependently delayed while 0.8 and 2.4 μg/tail of CGS 21680 accelerated closure of the wounds when compared to the control group treated with the solvent. The thickness and cell proliferation of the epithelial layer in the wounds were decreased by 2.5 μg/tail of ZM241385 but increased by 0.8 μg/tail of CGS 21680 at 3 days post wounding compared to the control group. To our knowledge, this is the first report demonstrating the effects of adenosine receptor activation on skin re-epithelization in vertebrates. Moreover, the effects of ZM241385 and CGS 21680 on granulation formation including fibroblast migration and collagen deposition in grass carp skin wounds were also investigated in the present study. The results revealed that these two compounds oppositely regulated fibroblast migration and collagen deposition in grass carp skin wounds. These results implied that activation of grass carp A<sub>2a</sub>R and A<sub>2b</sub>R improved granulation formation in the wound, leading to enhancement of skin wound repair in juvenile grass carp. These results provide the new clues and mechanisms on the skin wound healing in fish species.</div></div>","PeriodicalId":8375,"journal":{"name":"Aquaculture","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aquaculture","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0044848624011360","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"FISHERIES","Score":null,"Total":0}
引用次数: 0
Abstract
Wounded fish skin leads to the impairment of internal tissue homeostasis and provides an opportunity for pathogens to invade, resulting in the occurrence of fish diseases. Accordingly, skin wound healing has been investigated in many fishes. In the present study, we found that the concentration of adenosine increased in grass carp skin wounds and antagonization of adenosine receptors aggravated the skin wound closure, implying that adenosine receptor activation played a role in fish skin wound repair. After the expression of adenosine A2a receptor (A2aR) and A2bR in grass carp skin was verified, the effects of two adenosine analogs, ZM241385 and CGS 21680, on grass carp A2aR and A2bR activation were examined by a dual-luciferase assay. The results showed that 500 nM of ZM241385 could antagonize the activation of both receptors by adenosine and 5–5000 nM of CGS 21680 could stimulate both receptors. In this scenario, these two compounds were administrated to the skin wounds of juvenile grass carp weighting about 8.0 g each, showing that 0.5, 2.5, 12.5 μg/tail of ZM241385 dose-dependently delayed while 0.8 and 2.4 μg/tail of CGS 21680 accelerated closure of the wounds when compared to the control group treated with the solvent. The thickness and cell proliferation of the epithelial layer in the wounds were decreased by 2.5 μg/tail of ZM241385 but increased by 0.8 μg/tail of CGS 21680 at 3 days post wounding compared to the control group. To our knowledge, this is the first report demonstrating the effects of adenosine receptor activation on skin re-epithelization in vertebrates. Moreover, the effects of ZM241385 and CGS 21680 on granulation formation including fibroblast migration and collagen deposition in grass carp skin wounds were also investigated in the present study. The results revealed that these two compounds oppositely regulated fibroblast migration and collagen deposition in grass carp skin wounds. These results implied that activation of grass carp A2aR and A2bR improved granulation formation in the wound, leading to enhancement of skin wound repair in juvenile grass carp. These results provide the new clues and mechanisms on the skin wound healing in fish species.
期刊介绍:
Aquaculture is an international journal for the exploration, improvement and management of all freshwater and marine food resources. It publishes novel and innovative research of world-wide interest on farming of aquatic organisms, which includes finfish, mollusks, crustaceans and aquatic plants for human consumption. Research on ornamentals is not a focus of the Journal. Aquaculture only publishes papers with a clear relevance to improving aquaculture practices or a potential application.