Disease relevance of Tnxb

• Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome [1].
• Expression of TN-X was up-regulated to a higher degree in low-grade astrocytomas than in high-grade astrocytomas [2].
• Tumour invasion and metastasis are promoted in mice deficient in tenascin-X [3].
• Consequently, the melanoma cells inoculated in TNX-/- mice might facilitate invasion and metastasis [3].
• Osteosarcoma (MG63) and bladder carcinoma cells (ECV304) cells were shown to adhere to purified TN-X, but did not spread and did not assemble actin stress fibers [4].

High impact information on Tnxb

• Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix [1].
• On Northern blots we detected a TN-X mRNA of approximately 13 kb in most tissues analyzed, whereas in various mouse cell lines mRNAs of approximately 11 and 13 kb were detected, suggesting the possibility of alternative splicing of TN-X transcripts [5].
• The TN-X mRNA as well as the protein are predominantly expressed in heart and skeletal muscle, but the mRNA is found in most tissues at a low level [5].
• Although the TN-X gene lies in the MHC class III locus, it is not expressed in the lymphoid organs analyzed, except for the staining around blood vessels [5].
• The TN-X gene lies in the major histocompatibility complex (MHC) class III region, as it is the case for its human counterpart [5].

Biological context of Tnxb

• Comparison also revealed that introns 1, 4 and 6 of Tnx are highly conserved between species [6].
• The sequence showed that mouse Tnx contains 43 exons separated by 42 introns [6].
• Induction of matrix metalloproteinase-2 by tenascin-X deficiency is mediated through the c-Jun N-terminal kinase and protein tyrosine kinase phosphorylation pathway [7].
• We have identified glucocorticoids as physiological inhibitors of tenascin-X and suggest that glucocorticoids may in part participate in the downregulation of tenascin-X in fibroblasts in vivo [8].
• CONCLUSION: TNX interacts with VEGF-B and enhances the ability of VEGF-B to stimulate cell proliferation [9].

Anatomical context of Tnxb

• We raised antibodies against mouse TN-X fragments expressed in bacteria and used these antibodies to identify the TN-X protein in heart cell extracts and in the conditioned medium of a renal carcinoma cell line [5].
• In skin and tissues of the digestive tract often a reciprocal distribution of TN-X and TN-C was observed [5].
• TN-X was mainly localized in the perivascular stroma around tumor vessels, and weakly expressed in the intercellular spaces among tumor cells [2].
• To determine whether TNX plays a part in tumour invasion and metastasis and to disclose its normal physiological role, we disrupted its gene in mouse embryonic stem cells by homologous recombination and created mice deficient in TNX [3].
• TNX-positive cells then gradually spread all over the entire surface of the heart and invaded and formed primitive vascular channels in the myocardium [10].

Associations of Tnxb with chemical compounds

• Steroid hormone glucocorticoids, were found to downregulate tenascin-X mRNA levels and protein synthesis in fibroblasts but not carcinoma cells at physiological concentrations [8].
• Tenascin-X (TNX) is an extracellular matrix glycoprotein [11].
• By thin-layer chromatography of total lipids, it was found that the level of triglyceride was significantly increased in TNX-/- mice [12].
• By gas chromatography-mass spectrometry analysis of triglyceride-associated fatty acids in the skin, saturated fatty acid palmitoic acid was decreased, whereas unsaturated fatty acids palmitoleic acid and oleic acid were increased in TNX-/- mice compared with those in wild-type mice [12].
• An increase in the saturated fatty acid stearic acid and decreases in the unsaturated fatty acids palmitoleic acid, oleic acid and linoleic acid, compared to those in mock-transfected cells were also caused by over-expression of TNX [12].

Regulatory relationships of Tnxb

• In this study, we investigated the molecular mechanism by which TNX deficiency activates the MMP-2 gene [7].

Other interactions of Tnxb

• Invasion of melanoma in double knockout mice lacking tenascin-X and tenascin-C [13].
• The elevated expression of MMP-2 and MMP-9 resulted in decreased laminin levels, to less than half that of wild-type mice in the homogenates of TNX-/- mice [3].
• It was found that the mRNA expression levels of type I collagen and collagen fibril-associated molecules other than decorin were decreased and that the expression level of decorin was increased in TNX-null fibroblasts [11].
• RESULTS: We used mouse TNX-specific fibronectin type III repeats (mTNX/FNIII13-25) as a bait for the screening [9].
• However, the organization of type VI collagen in the extracellular matrix of TNX-null fibroblasts was similar to that of wild-type fibroblasts [11].

Analytical, diagnostic and therapeutic context of Tnxb

• Full-length recombinant TNX, which is expressed in and purified from mammalian cell cultures, and type VI collagen purified from bovine placenta were used [14].
• Finally, we observed abnormally large collagen fibrils by electron microscopy in the skin from TNX-deficient (TNX-/-) mice during development [14].
• We investigated the deposition of tenascin-X and elastin into skin-equivalent in vitro and also in vivo after transplantation onto immunodeficient mice [15].
• We used biophysical measurements and immunofluorescence to study connective tissue properties in TNX knockout and wild-type mice [16].

References