Aggf1, the angiogenic factor with G-patch and FHA domain 1, is crucial for multiple biological processes. It regulates cell differentiation, proliferation, migration, apoptosis, autophagy and endoplasmic reticulum stress. Aggf1 promotes vasculogenesis and angiogenesis, and is involved in signaling pathways such as mTOR-S6K-ERK1/2, TGF-β1, and NF-κB, playing a significant role in the development of the circulation system and in maintaining tissue homeostasis [2,3].

In gene knockout studies, Aggf1 -/- zebra fish showed impaired specification of hemangioblasts and HSPCs, hematopoiesis, and vascular development, indicating Aggf1 acts at the top of npas4l during hemangioblast specification [3]. In mice, Aggf1+/- and VSMC-specific Aggf1smcKO knockout mice had aggravated thoracic aortic aneurysm (TAA) phenotypes. Mechanistically, AGGF1 enhances integrin α7-LAP-TGF-β1 interaction, blocking mature TGF-β1 formation and inhibiting Smad2/3 and ERK1/2 phosphorylation in VSMCs [1]. Also, Aggf1+/- mice had exacerbated skeletal muscle atrophy phenotypes, and AGGF1 protein injection attenuated atrophy by promoting autophagy and inhibiting MuRF1 expression through the AGGF1-TWEAK/Fn14-NF-κB pathway [2].

In conclusion, Aggf1 is essential for processes like hemangioblast specification, angiogenesis, and tissue homeostasis. Gene knockout mouse models have revealed its role in diseases such as TAA and skeletal muscle atrophy, highlighting its potential as a therapeutic target for these conditions.

References:

1. Da, Xingwen, Li, Ziyan, Huang, Xiaofan, Yao, Yufeng, Wang, Qing K. 2023. AGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling. In Nature communications, 14, 2265. doi:10.1038/s41467-023-37809-x. https://pubmed.ncbi.nlm.nih.gov/37081014/

2. He, Zuhan, Song, Qixue, Yu, Yubing, Yao, Yufeng, Wang, Qing K. 2023. Protein therapy of skeletal muscle atrophy and mechanism by angiogenic factor AGGF1. In Journal of cachexia, sarcopenia and muscle, 14, 978-991. doi:10.1002/jcsm.13179. https://pubmed.ncbi.nlm.nih.gov/36696895/

3. Yang, Zhongcheng, Guo, Di, Zhao, Jinyan, Ke, Tie, Wang, Qing K. 2023. Aggf1 Specifies Hemangioblasts at the Top of Regulatory Hierarchy via Npas4l and mTOR-S6K-Emp2-ERK Signaling. In Arteriosclerosis, thrombosis, and vascular biology, 43, 2348-2368. doi:10.1161/ATVBAHA.123.318818. https://pubmed.ncbi.nlm.nih.gov/37881938/