Marine-derived STING inhibitors, excavatolide B promote wound repair in full-thickness-incision rats.

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Auteurs principaux: Chang, Chun-Kai, Wu, Zong-Sheng, Niu, Guang-Hao, Chou, Yu-Yu, Tang, Shih-Hsuan, Zhang, Mingzi M, Sung, Chun-Sung, Tung, Hsiang-Ting, Tsou, Lun Kelvin, Tang, Chi-Chieh, Sung, Ping-Jyun, Lo, Yi-Hao, Wen, Zhi-Hong
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Langue:en
Publié: International immunopharmacology 2025
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author Chang, Chun-Kai
Wu, Zong-Sheng
Niu, Guang-Hao
Chou, Yu-Yu
Tang, Shih-Hsuan
Zhang, Mingzi M
Sung, Chun-Sung
Tung, Hsiang-Ting
Tsou, Lun Kelvin
Tang, Chi-Chieh
Sung, Ping-Jyun
Lo, Yi-Hao
Wen, Zhi-Hong
author_facet Chang, Chun-Kai
Wu, Zong-Sheng
Niu, Guang-Hao
Chou, Yu-Yu
Tang, Shih-Hsuan
Zhang, Mingzi M
Sung, Chun-Sung
Tung, Hsiang-Ting
Tsou, Lun Kelvin
Tang, Chi-Chieh
Sung, Ping-Jyun
Lo, Yi-Hao
Wen, Zhi-Hong
Chang, Chun-Kai
Wu, Zong-Sheng
Niu, Guang-Hao
Chou, Yu-Yu
Tang, Shih-Hsuan
Zhang, Mingzi M
Sung, Chun-Sung
Tung, Hsiang-Ting
Tsou, Lun Kelvin
Tang, Chi-Chieh
Sung, Ping-Jyun
Lo, Yi-Hao
Wen, Zhi-Hong
collection PubMed - marine biology
contents Marine-derived STING inhibitors, excavatolide B promote wound repair in full-thickness-incision rats. Chang, Chun-Kai Wu, Zong-Sheng Niu, Guang-Hao Chou, Yu-Yu Tang, Shih-Hsuan Zhang, Mingzi M Sung, Chun-Sung Tung, Hsiang-Ting Tsou, Lun Kelvin Tang, Chi-Chieh Sung, Ping-Jyun Lo, Yi-Hao Wen, Zhi-Hong Animals Wound Healing Humans Rats Male Membrane Proteins Rats, Sprague-Dawley Anti-Inflammatory Agents Skin Cell Line Signal Transduction Fibroblasts Cell Proliferation Cell Movement STING Protein The process of wound healing encompasses both inflammatory and proliferative stages. Excessive inflammation is known to impede the healing of chronic wounds. Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway causes inflammation during cellular stress and tissue damage. Herein, we examined the anti-inflammatory effects of the marine-derived STING antagonist excavatolide B (EXCB) and its derivatives, EXCB-61 and EXCB-79, in full-thickness-incision rats. Wound area measurements, histopathological observations, and immunohistochemical analyses were performed to evaluate the roles of these compounds in wound healing. These three compounds were found to have low toxicity, with EXCB promoting Hs68 human dermal fibroblast migration and proliferation. EXCB and EXCB61 treatments, but not EXCB79, reduced the wound area. The histopathological results showed a significant decrease in immune cell infiltration and mast cell accumulation in all compound-treated groups. Immunohistochemical analysis revealed that EXCB and its derivatives reduced cGAS-STING pathway factors such as STING, phosphorylated TANK-binding kinase 1, nuclear factor kappa-light-chain-enhancer of activated B cells, and M1 macrophages while increasing the expression of angiogenic factors vascular endothelial growth factor and CD31, as well as M2 macrophages and collagen I/III deposition. We conclude that marine-derived STING antagonists can attenuate inflammatory responses by inhibiting the cGAS-STING pathway and promoting angiogenesis, thereby aiding wound healing.
format Artículo científico
id pubmed_40209311
institution PubMed
language en
publishDate 2025
publisher International immunopharmacology
record_format pubmed
spellingShingle Marine-derived STING inhibitors, excavatolide B promote wound repair in full-thickness-incision rats.
Chang, Chun-Kai
Wu, Zong-Sheng
Niu, Guang-Hao
Chou, Yu-Yu
Tang, Shih-Hsuan
Zhang, Mingzi M
Sung, Chun-Sung
Tung, Hsiang-Ting
Tsou, Lun Kelvin
Tang, Chi-Chieh
Sung, Ping-Jyun
Lo, Yi-Hao
Wen, Zhi-Hong
Animals
Wound Healing
Humans
Rats
Male
Membrane Proteins
Rats, Sprague-Dawley
Anti-Inflammatory Agents
Skin
Cell Line
Signal Transduction
Fibroblasts
Cell Proliferation
Cell Movement
STING Protein
Marine-derived STING inhibitors, excavatolide B promote wound repair in full-thickness-incision rats. Chang, Chun-Kai Wu, Zong-Sheng Niu, Guang-Hao Chou, Yu-Yu Tang, Shih-Hsuan Zhang, Mingzi M Sung, Chun-Sung Tung, Hsiang-Ting Tsou, Lun Kelvin Tang, Chi-Chieh Sung, Ping-Jyun Lo, Yi-Hao Wen, Zhi-Hong Animals Wound Healing Humans Rats Male Membrane Proteins Rats, Sprague-Dawley Anti-Inflammatory Agents Skin Cell Line Signal Transduction Fibroblasts Cell Proliferation Cell Movement STING Protein The process of wound healing encompasses both inflammatory and proliferative stages. Excessive inflammation is known to impede the healing of chronic wounds. Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway causes inflammation during cellular stress and tissue damage. Herein, we examined the anti-inflammatory effects of the marine-derived STING antagonist excavatolide B (EXCB) and its derivatives, EXCB-61 and EXCB-79, in full-thickness-incision rats. Wound area measurements, histopathological observations, and immunohistochemical analyses were performed to evaluate the roles of these compounds in wound healing. These three compounds were found to have low toxicity, with EXCB promoting Hs68 human dermal fibroblast migration and proliferation. EXCB and EXCB61 treatments, but not EXCB79, reduced the wound area. The histopathological results showed a significant decrease in immune cell infiltration and mast cell accumulation in all compound-treated groups. Immunohistochemical analysis revealed that EXCB and its derivatives reduced cGAS-STING pathway factors such as STING, phosphorylated TANK-binding kinase 1, nuclear factor kappa-light-chain-enhancer of activated B cells, and M1 macrophages while increasing the expression of angiogenic factors vascular endothelial growth factor and CD31, as well as M2 macrophages and collagen I/III deposition. We conclude that marine-derived STING antagonists can attenuate inflammatory responses by inhibiting the cGAS-STING pathway and promoting angiogenesis, thereby aiding wound healing.
title Marine-derived STING inhibitors, excavatolide B promote wound repair in full-thickness-incision rats.
topic Animals
Wound Healing
Humans
Rats
Male
Membrane Proteins
Rats, Sprague-Dawley
Anti-Inflammatory Agents
Skin
Cell Line
Signal Transduction
Fibroblasts
Cell Proliferation
Cell Movement
STING Protein
url https://pubmed.ncbi.nlm.nih.gov/40209311/