Ahsg-KO Mouse

Ahsg, also known as Alpha 2-Heremans Schmid Glycoprotein or Fetuin-A, is a multifunctional plasma agent mainly synthesized by the liver in adult humans [3,4]. It plays roles in multiple biological processes, such as acting as a physiological inhibitor of insulin receptor tyrosine kinase associated with insulin resistance, a negative acute-phase reactant, and regulating bone remodeling and calcium metabolism by inhibiting calcium salt precipitation and vascular calcifications [3].

In terms of disease-related findings, in multiple sclerosis, a per standard deviation increase in plasma AHSG has a protective effect, with an odds ratio of 0.88 (95% CI, 0.83-0.94), suggesting it could be a potential drug target [1]. In lung adenocarcinoma, AHSG expression is significantly higher in cancer tissues compared to normal tissues. High AHSG expression is associated with a worse overall survival duration, and it promotes tumour proliferation, migration, and invasion, thus may be a prognostic factor and potential treatment target [2]. In bladder cancer, AHSG expression is higher in cancer cells and tissues, and it promotes cell proliferation by regulating the TGF-β signalling pathway, potentially serving as a novel marker [5]. In ovarian cancer, AHSG in exosomes from ascites inhibits the malignant progression of ovarian cancer by regulating the p53/FAK/Src signalling pathway, making it a potential candidate for treatment [6].

In conclusion, Ahsg is a multifunctional protein involved in insulin regulation, calcium metabolism, and other processes. Its role in multiple diseases, including multiple sclerosis, lung adenocarcinoma, bladder cancer, and ovarian cancer, has been revealed through various studies. Understanding Ahsg's functions provides insights into disease mechanisms and potential treatment strategies.

References:

1. Lin, Jianfeng, Zhou, Jiawei, Xu, Yan. . Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis. In Brain : a journal of neurology, 146, 3364-3372. doi:10.1093/brain/awad070. https://pubmed.ncbi.nlm.nih.gov/36864689/

2. Xing, Xiaoying, Cao, Fumin, Gao, Liping, Song, Minglei. 2023. AHSG, a Gene Promoting Tumour Proliferation, Migration and Invasion, is an Independent Prognostic Factor for Poor Overall Survival in Lung Adenocarcinoma. In Molecular biology reports, 50, 7659-7666. doi:10.1007/s11033-023-08623-x. https://pubmed.ncbi.nlm.nih.gov/37535244/

3. Dabrowska, Anna Maria, Tarach, Jerzy Stanislaw, Wojtysiak-Duma, Beata, Duma, Dariusz. 2015. Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature. In Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia, 159, 352-9. doi:10.5507/bp.2015.018. https://pubmed.ncbi.nlm.nih.gov/25916279/

4. Ochieng, Josiah, Nangami, Gladys, Sakwe, Amos, Thomas, Portia, Lammers, Philip. 2018. Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes. In International journal of molecular sciences, 19, . doi:10.3390/ijms19082211. https://pubmed.ncbi.nlm.nih.gov/30060600/

5. Dong, Yufei, Ding, Dapeng, Gu, Juebin, Chen, Mingying, Li, Shijun. . Alpha-2 Heremans Schmid Glycoprotein (AHSG) promotes the proliferation of bladder cancer cells by regulating the TGF-β signalling pathway. In Bioengineered, 13, 14282-14298. doi:10.1080/21655979.2022.2081465. https://pubmed.ncbi.nlm.nih.gov/35746836/

6. Xie, Guangyan, Zhang, Yongli, Ma, Jiachen, Zhang, Bei, Zhou, Xueyan. 2024. Exosomal AHSG in ovarian cancer ascites inhibits malignant progression of ovarian cancer by p53/FAK/Src signaling. In Translational cancer research, 13, 5365-5380. doi:10.21037/tcr-24-789. https://pubmed.ncbi.nlm.nih.gov/39525039/