Bves, also known as Blood Vessel Epicardial Substance, is an evolutionarily conserved transmembrane protein. It is postulated to play roles in cell adhesion, cell motility, and junctional signaling. Bves is expressed in cardiac, skeletal, and gastrointestinal epithelial tissues. It is involved in regulating molecular pathways such as cAMP, WNT, and promoting the degradation of the oncogene c-Myc [1,2,3].

Mouse models have been crucial in understanding Bves' functions. BVES-knockout (BVES-KO) mice sustain worse intestinal injury and inflammation, and loss of BVES promotes tumor formation in the gastrointestinal tract [2]. In muscular dystrophy, BVES deletion in mice reduces muscle mass and impairs muscle performance, while virally delivered BVES reverses these defects, indicating its role in maintaining muscle mass and function through negative regulation of adenylyl cyclase 9-mediated cAMP signaling [4]. Systemic AAV9-BVES delivery in BVES-KO mice, a model of LGMDR25, ameliorates muscular dystrophy features, showing potential for gene therapy [5]. Also, in a rat model of graft arteriosclerosis, genetic knockdown and overexpression of Bves in vascular smooth muscle cells (VSMCs) revealed its role in maintaining the VSMC contractile phenotype and protecting against transplant vasculopathy [6].

In conclusion, Bves is essential for maintaining tissue integrity and homeostasis in multiple tissues. Studies using gene-knockout mouse models have revealed its significance in intestinal epithelium regulation, suppression of tumorigenesis, muscle homeostasis, and prevention of transplant vasculopathy. These findings contribute to understanding the mechanisms of related diseases and potentially developing therapeutic strategies [2,4,5,6].

References:

1. Hager, H A, Bader, D M. . Bves: ten years after. In Histology and histopathology, 24, 777-87. doi:10.14670/HH-24.777. https://pubmed.ncbi.nlm.nih.gov/19337975/

2. Parang, Bobak, Thompson, Joshua J, Williams, Christopher S. 2018. Blood Vessel Epicardial Substance (BVES) in junctional signaling and cancer. In Tissue barriers, 6, 1-12. doi:10.1080/21688370.2018.1499843. https://pubmed.ncbi.nlm.nih.gov/30307367/

3. Osler, Megan E, Smith, Travis K, Bader, David M. . Bves, a member of the Popeye domain-containing gene family. In Developmental dynamics : an official publication of the American Association of Anatomists, 235, 586-93. doi:. https://pubmed.ncbi.nlm.nih.gov/16444674/

4. Li, Haiwen, Wang, Peipei, Zhang, Chen, Zhou, Yuan, Han, Renzhi. 2023. Defective BVES-mediated feedback control of cAMP in muscular dystrophy. In Nature communications, 14, 1785. doi:10.1038/s41467-023-37496-8. https://pubmed.ncbi.nlm.nih.gov/36997581/

5. Li, Haiwen, Wang, Peipei, Hsu, Ethan, Stanford, Kristin I, Han, Renzhi. 2022. Systemic AAV9.BVES delivery ameliorates muscular dystrophy in a mouse model of LGMDR25. In Molecular therapy : the journal of the American Society of Gene Therapy, 31, 398-408. doi:10.1016/j.ymthe.2022.11.012. https://pubmed.ncbi.nlm.nih.gov/36433649/

6. Liu, Jin-Xin, Huang, Tong, Xie, Dawei, Yu, Qihong. 2022. Bves maintains vascular smooth muscle cell contractile phenotype and protects against transplant vasculopathy via Dusp1-dependent p38MAPK and ERK1/2 signaling. In Atherosclerosis, 357, 20-32. doi:10.1016/j.atherosclerosis.2022.08.010. https://pubmed.ncbi.nlm.nih.gov/36037759/