Tnxb, encoding tenascin-X, is an extracellular matrix protein. It is involved in multiple biological processes, and its functions are related to various signaling pathways. For example, it plays a role in the regulation of endothelial-to-mesenchymal transition (EndMT), which is a critical driver of vascular inflammation and atherosclerosis, and is associated with the TGF-β signaling pathway [1].

In endothelium-specific Tnxb knockout (EC-Tnxb-KO) mice, increased endothelial TGF-β signaling, elevated endothelial expression of EndMT and inflammatory marker genes were observed. When subjected to partial carotid artery ligation, these mice showed increased vascular remodeling. Crossed to low-density lipoprotein receptor-deficient mice and fed a high-fat diet, they had advanced atherosclerotic lesions. Treatment with an anti-TGF-beta antibody or additional endothelial loss of TGF-beta receptors 1 and 2 normalized endothelial TGF-beta signaling and prevented EndMT. In vitro, TN-X directly interacts with TGF-β through its fibrinogen-like domain, interfering with TGF-β binding to its receptor [1]. Also, in F8-/-mouse cartilage with Tnxb loss, it promoted cartilage degeneration and subchondral bone loss in hemophilic arthropathy, and Tnxb knockdown in chondrocytes promoted apoptosis and inhibited AKT phosphorylation [2].

In conclusion, Tnxb is a crucial factor in regulating vascular TGF-β-mediated processes like EndMT, endothelial inflammation, and atherogenesis. The study of Tnxb knockout mouse models has significantly advanced our understanding of its role in atherosclerosis and hemophilic arthropathy, providing potential targets for preventing vascular inflammation and treating hemophilic arthropathy [1,2].

References:

1. Liang, Guozheng, Wang, ShengPeng, Shao, Jingchen, Wang, Lei, Offermanns, Stefan. 2022. Tenascin-X Mediates Flow-Induced Suppression of EndMT and Atherosclerosis. In Circulation research, 130, 1647-1659. doi:10.1161/CIRCRESAHA.121.320694. https://pubmed.ncbi.nlm.nih.gov/35443807/

2. Chen, Jiali, Zeng, Qinghe, Wang, Xu, Tong, Peijian, Jin, Hongting. 2024. Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling. In eLife, 13, . doi:10.7554/eLife.93087. https://pubmed.ncbi.nlm.nih.gov/38819423/