HGNC Approved Gene Symbol: VASN
Cytogenetic location: 16p13.3 Genomic coordinates (GRCh38) : 16:4,371,848-4,383,538 (from NCBI)
By screening a heart cDNA library using a signal sequence trap to identify cDNAs encoding secreted and type I membrane proteins, Ikeda et al. (2004) cloned vasorin. The deduced 673-amino acid protein contains a putative hydrophobic signal sequence, 10 tandem arrays of a leucine-rich repeat, an epidermal growth factor (131530)-like domain, a fibronectin (135600) type III-like domain, and a short intracellular region. Northern blot analysis of adult tissues detected highest expression of a 2.8-kb vasorin transcript in aorta, with moderate expression in kidney and placenta. In situ hybridization detected mouse vasorin in the tunica media of the proximal ascending aorta, descending thoracic aorta, abdominal aorta, and coronary arteries. In mouse kidney, vasorin was expressed in interstitial cells. Northern blot analysis and in situ hybridization of staged mouse embryos showed that expression of vasorin in aortas increased gradually in parallel with the differentiation of vascular smooth muscle cells beginning at embryonic day 10.5. Vasorin expressed by transfected Chinese hamster ovary cells showed an apparent molecular mass of 110 kD, which shifted following N-glycosidase treatment. Vasorin was expressed on the cell surface and was secreted into the culture medium.
Ikeda et al. (2004) found that vasorin expression was downregulated during the establishment of rat vascular smooth muscle cells in culture, and it was upregulated in a mouse embryonal carcinoma cell line following retinoic acid-induced differentiation into smooth muscle cells. Vasorin expression was also downregulated during vessel repair in the rat arterial balloon injury model. Reversing vasorin downregulation by gene transfer significantly diminished injury-induced vascular lesion formation, at least in part by inhibiting transforming growth factor-beta (TGFB) signaling in vivo. The extracellular domain of vasorin interacted directly with TGFB1 (190180), TGFB2 (190220), and TGFB3 (190230) and showed a similar binding affinity for each.
Ikeda, Y., Imai, Y., Kumagai, H., Nosaka, T., Morikawa, Y., Hisaoka, T., Manabe, I., Maemura, K., Nakaoka, T., Imamura, T., Miyazono, K., Komuro, I., Nagai, R., Kitamura, T. Vasorin, a transforming growth factor beta-binding protein expressed in vascular smooth muscle cells, modulates the arterial response to injury in vivo. Proc. Nat. Acad. Sci. 101: 10732-10737, 2004. [PubMed: 15247411] [Full Text: https://doi.org/10.1073/pnas.0404117101]