Azgp1, also known as Zinc-alpha2-glycoprotein (ZAG), is a multifunctional secreted glycoprotein. It has been implicated in various biological processes including metabolism, inflammation, and cancer-related mechanisms. In metabolism, it is associated with leptin-mediated STAT3 phosphorylation pathway, and in inflammation, it may be related to macrophage-mediated inflammatory responses. In cancer, it is involved in processes such as epithelial-mesenchymal transition (EMT), angiogenesis, and tumor cell proliferation and metastasis [1-10]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In POMC neuron-specific KO mouse models, deletion of Azgp1 increases susceptibility to diet-induced obesity, while overexpression reduces energy intake, raises energy expenditure, and improves insulin sensitivity, indicating its crucial role in energy homeostasis [1]. In periodontitis murine models, Azgp1-/-mice show reduced periodontal inflammation and alveolar bone loss, along with suppressed M1 macrophage polarization and pyroptosis, suggesting its role in aggravating periodontitis [2]. In prostate cancer, AZGP1-/-mice show higher blood vessel density in the prostate by 6 months, demonstrating that AZGP1 deficiency promotes angiogenesis [3].

In conclusion, Azgp1 plays essential roles in energy metabolism, inflammation, and cancer-related processes. The KO/CKO mouse models have significantly contributed to understanding its functions in these areas, such as in diet-induced obesity, periodontitis, and prostate cancer angiogenesis, providing insights into potential therapeutic targets for related diseases.

References:

1. Qiu, Sheng, Wu, Qinan, Wang, Hao, Li, Ling, Yang, Mengliu. 2024. AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation. In Nature communications, 15, 3377. doi:10.1038/s41467-024-47684-9. https://pubmed.ncbi.nlm.nih.gov/38643150/

2. Yang, S, Yin, Y, Sun, Y, Xu, X, Song, J. 2024. AZGP1 Aggravates Macrophage M1 Polarization and Pyroptosis in Periodontitis. In Journal of dental research, 103, 631-641. doi:10.1177/00220345241235616. https://pubmed.ncbi.nlm.nih.gov/38491721/

3. Wen, Ru M, Qiu, Zhengyuan, Marti, G Edward W, Pitteri, Sharon J, Brooks, James D. 2024. AZGP1 deficiency promotes angiogenesis in prostate cancer. In Journal of translational medicine, 22, 383. doi:10.1186/s12967-024-05183-x. https://pubmed.ncbi.nlm.nih.gov/38659028/