Disease relevance of Tnmd

• Using an adenovirus expression system, we utilized the forced expression and subsequent secretion of the human TeM C-terminal 116 amino acids (Ad-shTeM) in human umbilical vein endothelial cells (HUVECs) to assess the anti-angiogenic properties of TeM [1].
• In situ hybridization of the eye tissues revealed TeM mRNA in the tendon of the extraocular muscle, the sclerocornea, the lens fiber cells, and the ganglion cell layer, inner nuclear layer cells, and pigment epithelium of the retina [2].

High impact information on Tnmd

• Tnmd-deficient mice did not have changes in tendon vessel density, and mice lacking both Tnmd and ChM-I had normal retinal vascularization and neovascularization after oxygen-induced retinopathy [3].
• We analyzed Tnmd function in vivo and provide evidence that Tnmd is processed in vivo and that the proteolytically cleaved C-terminal domain can be found in tendon extracts [3].
• TeM transcripts have been found in hypovascular tissues such as tendons and ligaments but the biological activity of TeM has not yet been fully explored [1].
• A monoclonal antibody, designated TeM 106, that recognizes an intrinsic protein from the vacuole membrane (tonoplast) of cauliflower (Brassica oleracea L. var. botrytis) is described [4].
• Myodulin is a novel potential angiogenic factor in skeletal muscle [5].

Biological context of Tnmd

• METHODS: Gene expression and protein localization of TeM in mouse eyes were examined by Northern blot analysis, in situ hybridization, and immunohistochemical analysis [2].
• Production of a secreted form of TeM and ChM-I through adenoviral gene transfer caused effective autocrine suppression of cell proliferation and capillary-like morphogenesis of retina vascular endothelial cells [2].
• Our results suggest that myodulin may be a muscle angiogenic factor operating through direct cell-to-cell interactions [5].
• The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here [5].

Anatomical context of Tnmd

• Overexpression of myodulin fused to a FLAG peptide showed evidence of a muscle cell surface protein [5].
• Myodulin RNA messengers were found in muscle fibers and their tendon extensions [5].
• TeM turned out to be expressed specifically in other hypovascular structures in the mesenchyme, such as the epimysium, tendon, and ligaments [6].
• Co-culture experiments of myoblasts and cardiac vascular endothelial cells reveal that myodulin, either presented in yeast membranes or in liposomes after purification, increases the invasive potential of endothelial cells with a similar efficiency as when over-expressed in skeletal muscle cells [7].
• Here, we show that mouse myodulin can be expressed at the plasma membrane of Saccharomyces cerevisiae and purified [7].

Analytical, diagnostic and therapeutic context of Tnmd

• Western blot detected 40- and 45-kDa immunoreactive bands of TeM in the eye as differently glycosylated forms of the transmembrane protein [2].
• CONCLUSIONS: These results indicate a potential role for TeM in prevention of vascular invasion in the mouse eye and the possibility of both TeM and ChM-I as candidates for use in gene therapy approaches to treatment of ocular angiogenesis [2].
• Coculture experiments using C(2)C(12) mouse myoblasts or myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular endothelial cells revealed that myodulin had a very active role in the invasive action of endothelial cells, without any evidence of extracellular myodulin secretion [5].
• The molecular specificities of TeM 106 were preliminarily determined using electrophoretic transfer procedures (immunoblotting) [4].
• TeM 106 is an IgM which was shown by indirect immunofluorescence microscopy of frozen thin sections to bind specifically to the tonoplast of highly vacuolated cells as well as to the tonoplast of small vacuoles in meristematic cells [4].

References