Anxa1, also known as Annexin-A1, is a protein-coding gene. It is a Ca(2+)-regulated, phospholipid-dependent, membrane-binding protein that participates in diverse biological processes like cellular transduction, membrane aggregation, inflammation, phagocytosis, proliferation, differentiation, and apoptosis [4]. It is involved in multiple pathways, such as those related to inflammation regulation and cholesterol transport [3]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In a murine model of acute aortic dissection (AAD), systemic deficiency of Anxa1 markedly progressed AAD, while administration of Anxa1 mimetic peptide rescued the AAD phenotype. Transcriptomic studies showed that Anxa1 deficiency triggered the synthetic phenotype of vascular smooth muscle cells (VSMCs) via down-regulation of the JunB/MYL9 pathway, leading to elevated inflammation, enhanced matrix metalloproteinases production, and augmented elastin degradation [2]. In a study on cerebral ischemia-reperfusion injury, Tat-NTS peptide, which targets microglial Anxa1, led to a shift of Anxa1 subcellular localization from the nucleus to the cytoplasm, increased Anxa1 SUMOylation, and transformed microglia towards an anti-inflammatory phenotype. This ultimately reduced infarct volume, improved neurological function, and facilitated behavioral recovery in MCAO mice [1].

In conclusion, Anxa1 plays essential roles in regulating inflammation, cell phenotype switching, and has implications in diseases like acute aortic dissection and cerebral ischemia-reperfusion injury. Findings from Anxa1 KO/CKO mouse models have been crucial in revealing these disease-related functions, providing potential targets for therapeutic interventions in these disease areas.

References:

1. Zhou, Huijuan, Yan, Lulu, Huang, Hezhou, Sun, Ning, Shi, Jing. 2023. Tat-NTS peptide protects neurons against cerebral ischemia-reperfusion injury via ANXA1 SUMOylation in microglia. In Theranostics, 13, 5561-5583. doi:10.7150/thno.85390. https://pubmed.ncbi.nlm.nih.gov/37908731/

2. Zhou, Changping, Lin, Zhiyong, Cao, Huanhuan, Pan, Bing, Zheng, Lemin. . Anxa1 in smooth muscle cells protects against acute aortic dissection. In Cardiovascular research, 118, 1564-1582. doi:10.1093/cvr/cvab109. https://pubmed.ncbi.nlm.nih.gov/33757117/

3. Shen, Xin, Zhang, Shun, Guo, Zhu, Xing, Dongming, Chen, Wujun. 2020. The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis. In Molecular medicine (Cambridge, Mass.), 26, 84. doi:10.1186/s10020-020-00213-y. https://pubmed.ncbi.nlm.nih.gov/32894039/

4. Guo, Chunmei, Liu, Shuqing, Sun, Ming-Zhong. . Potential role of Anxa1 in cancer. In Future oncology (London, England), 9, 1773-93. doi:10.2217/fon.13.114. https://pubmed.ncbi.nlm.nih.gov/24156336/