Mechanisms of outer membrane protein Amuc_1100 of Akkermansia muciniphila attenuating intestinal ischemia⁃reperfusion injury through STING signaling pathway in mice
|更新时间:2026-11-05
|
Mechanisms of outer membrane protein Amuc_1100 of Akkermansia muciniphila attenuating intestinal ischemia⁃reperfusion injury through STING signaling pathway in mice
Medical Journal of Wuhan UniversityVol. 46, Issue 7, Pages: 836-841(2025)
PIAO Guangyu,SHI Yu,CHEN Rong,et al.Mechanisms of outer membrane protein Amuc_1100 of Akkermansia muciniphila attenuating intestinal ischemia⁃reperfusion injury through STING signaling pathway in mice[J].Medical Journal of Wuhan University,2025,46(07):836-841.
PIAO Guangyu,SHI Yu,CHEN Rong,et al.Mechanisms of outer membrane protein Amuc_1100 of Akkermansia muciniphila attenuating intestinal ischemia⁃reperfusion injury through STING signaling pathway in mice[J].Medical Journal of Wuhan University,2025,46(07):836-841.DOI: 10.14188/j.1671-8852.2024.0674.
Mechanisms of outer membrane protein Amuc_1100 of Akkermansia muciniphila attenuating intestinal ischemia⁃reperfusion injury through STING signaling pathway in mice
on intestinal ischemia⁃reperfusion (IIR) injury in mice.
Methods
2
Eighteen healthy m
ale adult C57BL/6J mice were randomly divided into three groups: Control (S group
n
=6)
IIR (IIR group
n
=6)
and IIR+Amuc_1100 pretreatment (IIR+Amuc_1100 group
n
=6). Mice in the IIR+Amuc_1100 group were pretreated with Amuc_1100 protein (3 µg•d
-1
) for 7 days. On the following day
IIR injury models were established by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion
and small intestine tissues were collected. Tissues were fixed and stained using standard HE staining procedures to observe tissue changes and perform Chiu's pathological damage score. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the intestinal tissues were measured. Western Blot was used to detect tight junction proteins expression and stimulator of interferons genes (STING) signaling pathway activation. ELISA was used to measure serum tumor necrosis factor (TNF)⁃α and interleukin (IL)⁃6 levels.
Results
2
Compared with the S group
the IIR group showed a significant increase in Chiu's score
decreased SOD activity
increased MDA production
and reduced tight junction protein expression. Amuc_1100 protein pretreatment significantly reduced the increase in Chiu's pathological damage score caused by IIR
increased SOD activity
decreased MDA production
and significantly increased tight junction protein expression. Additionally
Amuc_1100 pretreatment significantly reduced the IIR⁃induced overexpression of p⁃STING
p⁃TBK1
and p⁃NF⁃κB and decreased the elevated levels of TNF⁃α and IL⁃6 induced by IIR.
Conclusion
2
Amuc_1100 protein pretreatment alleviates intestinal ischemia⁃reperfusion injury
possibly through the inhibition of STING signaling pathway.
关键词
Keywords
references
COLLARD C D , GELMAN S . Pathophysiology, clinical manifestations, and prevention of ischemia⁃reperfusion injury [J ] . Anesthesiology , 2001 , 94 ( 6 ): 1133 ⁃ 1138 .
CHEN J Y , WANG Y , SHI Y X , et al . Association of gut microbiota with intestinal ischemia/reperfusion injury [J ] . Front Cell Infect Microbiol , 2022 , 12 : 962782 .
WANG Y H , YAN Z Z , LUO S D , et al . Gut microbiota⁃derived succinate aggravates acute lung injury after intestinal ischaemia/reperfusion in mice [J ] . Eur Respir J , 2023 , 61 ( 2 ): 2200840 .
DAI D , DAI F D , CHEN J C , et al . Integrated multi⁃omics reveal important roles of gut contents in intestinal ischemia⁃reperfusion induced injuries in rats [J ] . Commun Biol , 2022 , 5 ( 1 ): 938 .
TANG J L , ZHAO M C , MIAO X , et al . Bifidobacterium longum GL001 alleviates rat intestinal ischemia⁃reperfusion injury by modulating gut microbiota composition and intestinal tissue metabolism [J ] . Food Funct , 2024 , 15 ( 7 ): 3653 ⁃ 3668 .
ZHAO M Q , TANG F , HUANG X Y , et al . Polysaccharide isolated from Agaricus blazei murill alleviates intestinal ischemia/reperfusion injury through regulating gut microbiota and mitigating inflammation in mice [J ] . J Agric Food Chem , 2024 , 72 ( 4 ): 2202 ⁃ 2213 .
DENG F , LIN Z B , SUN Q S , et al . The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury [J ] . Int J Biol Sci , 2022 , 18 ( 10 ): 3981 ⁃ 3992 .
HAN B , CHAO K , WANG D , et al . A purified membrane protein from Akkermansia muciniphila blunted the sepsis⁃induced acute lung injury by modulation of gut microbiota in rats [J ] . Int Immunopharmacol , 2023 , 121 : 110432 .
YANG Y C , WANG L , Peugnet⁃González I , et al . cGAS⁃STING signaling pathway in intestinal homeostasis and diseases [J ] . Front Immunol , 2023 , 14 : 1239142 .
DECOUT A , KATZ J D , VENKATRAMAN S , et al . The cGAS⁃STING pathway as a therapeutic target in inflammatory diseases [J ] . Nat Rev Immunol , 2021 , 21 ( 9 ): 548 ⁃ 569 .
HU X L , ZHANG H J , ZHANG Q X , et al . Emerging role of STING signalling in CNS injury: Inflammation, autophagy, necroptosis, ferroptosis and pyroptosis [J ] . J Neuroinflammation , 2022 , 19 ( 1 ): 242 .
PLOVIER H , EVERARD A , DRUART C , et al . A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice [J ] . Nat Med , 2017 , 23 ( 1 ): 107 ⁃ 113 .
CHEN S J , QIAN K Y , ZHANG G H , et al . Akkermansia muciniphila and its outer membrane protein Amuc_1100 prophylactically attenuate 5⁃fluorouracil⁃induced intestinal mucositis [J ] . Biochem Biophys Res Commun , 2022 , 614 : 34 ⁃ 40 .
MENG Q T , CHEN R , LIU H M , et al . Role of inflammatory mediators regulated by Nrf2 in intestinal ischemia⁃reperfusion induced kidney injury in rats [J ] . Med J Wuhan Univ , 2017 , 38 ( 2 ): 189 ⁃ 192 .
WANG Y H . The role and mechanisms of gut microbiota metabolite succinate on acute lung injury induced by intestinal ischemia⁃reperfusion [D ] . Guangzhou : Southern Medical University , 2023 .
GU Z Y , PEI W L , SHEN Y H , et al . Akkermansia muciniphila and its outer protein Amuc_1100 regulates tryptophan metabolism in colitis [J ] . Food Funct , 2021 , 12 ( 20 ): 10184 ⁃ 10195 .
WANG L J , JIN Y L , PEI W L , et al . Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration [J ] . Acta Pharmacol Sin , 2024 , 45 ( 3 ): 570 ⁃ 580 .
GAO W W , WANG X , GUAN P . Research progress on the correlation between cGAS⁃STING signaling pathway and intestinal barrier dysfunction in sepsis [J ] . Chin J N Clin Med , 2023 , 16 ( 1 ): 102 ⁃ 106 .
WU J , LIU Q J , ZHANG X F , et al . STING⁃dependent induction of lipid peroxidation mediates intestinal ischemia⁃reperfusion injury [J ] . Free Radic Biol Med , 2021 , 163 : 135 ⁃ 140 .