ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditions
Abstract Diabetes mellitus is one of the risk factors for periodontitis. Patients with diabetes mellitus possess higher prevalence of periodontitis, more severe periodontal destruction, yet the underlying mechanisms of action are not yet clear. Annexin A2 (ANXA2) is a calcium-dependent phospholipid-...
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Nature Portfolio
2025-05-01
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| author | Yanlin Huang Zejing Qiu Chunhui Jiang Qian Fang Jiaye Wang Mingfang Han Yizhao Liu Zehui Li |
| author_facet | Yanlin Huang Zejing Qiu Chunhui Jiang Qian Fang Jiaye Wang Mingfang Han Yizhao Liu Zehui Li |
| author_sort | Yanlin Huang |
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| description | Abstract Diabetes mellitus is one of the risk factors for periodontitis. Patients with diabetes mellitus possess higher prevalence of periodontitis, more severe periodontal destruction, yet the underlying mechanisms of action are not yet clear. Annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein widely involved in membrane repair, cytokinesis, and endocytosis. In this study, we explore whether ANXA2 is one of the associative links between diabetes and periodontitis and find out its underlying mechanisms. Cellular senescence and mitochondrial functions (ROS, mitochondrial morphology, mitochondrial autophagy) were observed. We observed that ANXA2 expression was down-regulated in Periodontal ligament cells (PDLCs) under high glucose conditions. Furthermore, overexpression of ANXA2 delayed high glucose-induced cellular senescence and mitochondrial dysfunction. β-galactosidase activity and the mRNA levels of the senescence-relative genes(p21,p16) were decreased, mitochondrial fracture and ROS release were reduced, and the expression of mitochondrial autophagy-related proteins (LC3,p62,Parkin) was enhanced. expression was enhanced. Mechanistically, we demonstrated that it can regulate the AKT/eNOS signaling pathway by knockdown and overexpression of ANXA2 which was measured using Western blotting (WB) assay to measure the expression of eNOS, p-eNOS Ser1177, Akt and p-Akt Ser473 proteins in PDLCs. After that, we used AKT and eNOS inhibitors to demonstrate the protective effect of ANXA2 on PDLCs under high glucose conditions. The above results suggest that ANXA2 has an anti-aging protective effect, attenuates high glucose-induced cellular senescence in PDLCs, and maintains mitochondrial homeostasis. Therefore, it would be valuable to further explore its role in the link between diabetes and periodontitis in future experiments. |
| format | Article |
| id | doaj-art-8987c1c8367d4f97bfffc7b5e0cd9d37 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-8987c1c8367d4f97bfffc7b5e0cd9d372025-08-20T03:09:35ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-00950-2ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditionsYanlin Huang0Zejing Qiu1Chunhui Jiang2Qian Fang3Jiaye Wang4Mingfang Han5Yizhao Liu6Zehui Li7Department of stomatology, The Affiliated Hospital of Hangzhou Normal UniversityFaculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and TechnologyDepartment of stomatology, The Affiliated Hospital of Hangzhou Normal UniversityDepartment of stomatology, The Affiliated Hospital of Hangzhou Normal UniversityDepartment of stomatology, The Affiliated Hospital of Hangzhou Normal UniversityDepartment of stomatology, The Affiliated Hospital of Hangzhou Normal UniversityDepartment of stomatology, The Affiliated Hospital of Hangzhou Normal UniversityDepartment of stomatology, The Affiliated Hospital of Hangzhou Normal UniversityAbstract Diabetes mellitus is one of the risk factors for periodontitis. Patients with diabetes mellitus possess higher prevalence of periodontitis, more severe periodontal destruction, yet the underlying mechanisms of action are not yet clear. Annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein widely involved in membrane repair, cytokinesis, and endocytosis. In this study, we explore whether ANXA2 is one of the associative links between diabetes and periodontitis and find out its underlying mechanisms. Cellular senescence and mitochondrial functions (ROS, mitochondrial morphology, mitochondrial autophagy) were observed. We observed that ANXA2 expression was down-regulated in Periodontal ligament cells (PDLCs) under high glucose conditions. Furthermore, overexpression of ANXA2 delayed high glucose-induced cellular senescence and mitochondrial dysfunction. β-galactosidase activity and the mRNA levels of the senescence-relative genes(p21,p16) were decreased, mitochondrial fracture and ROS release were reduced, and the expression of mitochondrial autophagy-related proteins (LC3,p62,Parkin) was enhanced. expression was enhanced. Mechanistically, we demonstrated that it can regulate the AKT/eNOS signaling pathway by knockdown and overexpression of ANXA2 which was measured using Western blotting (WB) assay to measure the expression of eNOS, p-eNOS Ser1177, Akt and p-Akt Ser473 proteins in PDLCs. After that, we used AKT and eNOS inhibitors to demonstrate the protective effect of ANXA2 on PDLCs under high glucose conditions. The above results suggest that ANXA2 has an anti-aging protective effect, attenuates high glucose-induced cellular senescence in PDLCs, and maintains mitochondrial homeostasis. Therefore, it would be valuable to further explore its role in the link between diabetes and periodontitis in future experiments.https://doi.org/10.1038/s41598-025-00950-2MitochondriaCellular senescenceMitophagyDiabetesPeriodontitis |
| spellingShingle | Yanlin Huang Zejing Qiu Chunhui Jiang Qian Fang Jiaye Wang Mingfang Han Yizhao Liu Zehui Li ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditions Scientific Reports Mitochondria Cellular senescence Mitophagy Diabetes Periodontitis |
| title | ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditions |
| title_full | ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditions |
| title_fullStr | ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditions |
| title_full_unstemmed | ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditions |
| title_short | ANXA2 regulates mitochondrial function and cellular senescence of PDLCs via AKT/eNOS signaling pathway under high glucose conditions |
| title_sort | anxa2 regulates mitochondrial function and cellular senescence of pdlcs via akt enos signaling pathway under high glucose conditions |
| topic | Mitochondria Cellular senescence Mitophagy Diabetes Periodontitis |
| url | https://doi.org/10.1038/s41598-025-00950-2 |
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