Overexpression of mitofusin 2 ameliorates inflammation and oxidative stress in lipopolysaccharide-induced mastitis model by regulating phosphofurin acidic cluster sorting protein 2OA
Background:Mastitis seriously affects the mammary health of humans and animals.Studies have found that inflammation and oxidative stress play key roles in the occur-rence and development of mastitis.Therefore,in-depth research on related molecular mechanisms is of great significance.Methods:Postpartum mice were anesthetized with pentobarbital and administered lipopolysaccharide to develop the mouse mastitis model.Proteomic analysis was per-formed to compare protein expression in mitochondria-associated endoplasmic retic-ulum membranes(MAM)from two mouse mammary gland groups.Western blot was used to detect the expression of MAM-related proteins in mitochondria.AlphaFold3 was used to predict the molecular structures of phosphofurin acidic cluster sorting protein 2(PACS2)and mitofusin 2(MFN2)and their interaction levels.The MFN2-PACS2 interaction was investigated using co-immunoprecipitation and small interfer-ing RNA.Results:The results showed that the inflammation level in the mammary gland tissue of mice with mastitis significantly increased,the total antioxidant capacity decreased,and the expression of MAM-related proteins MFN2 and PACS2 was significantly downregulated.In cell experiments,overexpression of MFN2 can inhibit inflamma-tion and oxidative stress responses,and promote the interaction between MFN2 and PACS2 to affect the formation of MAMs.Conclusion:In summary,this study suggests that mastitis can alter the expression of MAM-related proteins in mouse breast tissue.The interaction between MFN2 and PACS2 regulates the formation of MAMs.Overexpression of MFN2 can promote the formation of MAMs and inhibit inflammation and oxidative stress response in mam-mary epithelial cells.Our results provided a new theoretical basis and potential thera-peutic targets for the prevention and treatment of mastitis.
Xiechen Zhou;Yufei Zhang;He Ma;Shoupeng Fu;Juxiong Liu;Wenjin Guo;Xiaofeng Tian;Bingxu Huang
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Key Laboratory for Zoonosis Research of the Ministry of Education,Institute of Zoonosis,College of Veterinary Medicine,Jilin University,Changchun,China Heilongjiang Dabeinong Agriculture and Animal Husbandry Food Company Limited,Harbin,Heilongjiang Province,ChinaState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Key Laboratory for Zoonosis Research of the Ministry of Education,Institute of Zoonosis,College of Veterinary Medicine,Jilin University,Changchun,ChinaState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Key Laboratory for Zoonosis Research of the Ministry of Education,Institute of Zoonosis,College of Veterinary Medicine,Jilin University,Changchun,ChinaState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Key Laboratory for Zoonosis Research of the Ministry of Education,Institute of Zoonosis,College of Veterinary Medicine,Jilin University,Changchun,ChinaState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Key Laboratory for Zoonosis Research of the Ministry of Education,Institute of Zoonosis,College of Veterinary Medicine,Jilin University,Changchun,ChinaState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Key Laboratory for Zoonosis Research of the Ministry of Education,Institute of Zoonosis,College of Veterinary Medicine,Jilin University,Changchun,ChinaDepartment of General Surgery,China-Japan Union Hospital of Jilin University,Changchun,ChinaDepartment of Laboratory Animals,College of Animal Sciences,Jilin University,Changchun,China State Key Laboratory of Animal Nutrition,College of Animal Science and Technology,China Agricultural University,Beijing,China Key Laboratory of Feed Synthetic Biotechnology,Ministry of Agriculture and Rural Affairs,Foshan Bo''en Biotechnology Co.,Ltd.,Foshan City,Guangdong Province,P.R.China
农业科技
mastitismitochondria-associated endoplasmic reticulum membranes(MAM)mitofusin 2(MFN2)phosphofurin acidic cluster sorting protein 2(PACS2)
《Animal Models and Experimental Medicine》 2026 (1)
P.154-167,14
National Natural Science Foundation of China,Grant/Award Number:32302826 and 32372961Jilin Provincial Special Project for Health Research Talents,Grant/Award Number:2020SCZ40China Postdoctoral Science Foundation,Grant/Award Number:2023M740623。
评论