Disease relevance of Tnc

• Progression of pulmonary hypertension is associated with increased serine elastase activity and the proteinase-dependent deposition of the extracellular matrix smooth muscle cell survival factor tenascin-C (refs. 1,2) [1].
• Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease [2].
• In injured brain the expression of tenascin-C has been correlated with the glial reaction since it was observed in regions suffering a dramatic glial proliferation and hypertrophy [3].
• Injections of 5,7-dihydroxytryptamine (5,7-DHT) in the dorsal and medial raphe nuclei, producing a partial loss of 5-HT neurons, induced rapid and transient increases in glial fibrillary acidic protein immunoreactivity indicative of a reactive gliosis, but no changes in the S100beta or tenascin-C normally secreted by astroglial cells [4].
• Highly malignant gliomas with poor prognosis exhibit high levels of Tn-C expression [5].

High impact information on Tnc

• Pulmonary artery pressure and muscularization were reduced by myocyte apoptosis and loss of extracellular matrix, specifically elastin and tenascin-C [1].
• Recent organ culture studies using hypertrophied rat pulmonary arteries have shown that elastase inhibitors suppress tenascin-C and induce smooth muscle cell apoptosis [1].
• We investigated the binding of the purified sodium channel and the extracellular domain of the beta2 subunit to tenascin-C and tenascin-R in vitro [6].
• Glutathione S-transferase-tagged fusion proteins containing various segments of tenascin-C and tenascin-R were purified, digested with thrombin to remove the epitope tag, immobilized on microtiter dishes, and tested for their ability to bind purified sodium channel or the epitope-tagged extracellular domain of beta2 subunits [6].
• Tenascin-C is induced with progressive pulmonary vascular disease in rats and is functionally related to increased smooth muscle cell proliferation [7].

Chemical compound and disease context of Tnc

• Retinoic acid and 1,25-dihydroxyvitamin D3 inhibit tenascin-C expression in rat glioma C6 cells [5].
• Here we demonstrate that Tn-C RNA expression in glioma C6 cells is inhibited in a dose-dependent manner by retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-D3) [5].
• Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts [8].

Biological context of Tnc

• Regression of hypertrophied rat pulmonary arteries in organ culture is associated with suppression of proteolytic activity, inhibition of tenascin-C, and smooth muscle cell apoptosis [9].
• These results suggest that mechanical injury induces boundary astrocytes to produce and release TNC that promotes cell proliferation and migration via integrin beta1 in an autocrine/paracrine fashion [10].
• Tenascin-C (TNC), an extracellular matrix glycoprotein, is involved in tissue morphogenesis like embryogenesis, wound healing or tumorigenesis [10].
• Using cultured SMCs, we found that the recombinant A1A2 protein that was found in the newly discovered Tn-C isoform promotes SMC chemotaxis [11].
• Tenascin-C (TNC), an extracellular matrix glycoprotein, is involved in tissue morphogenesis like embryogenesis, wound healing or tumorigenesis [12].

Anatomical context of Tnc

• Tenascin-C regulates proliferation and migration of cultured astrocytes in a scratch wound assay [10].
• Our results show novel expression patterns and cell associations of inhibitory CSPGs and tenascin-C that have important implications for axon regeneration across acute and chronic spinal cord scar tissue [13].
• A mechanism of impaired mobility of oligodendrocyte progenitor cells by tenascin C through modification of wnt signaling [14].
• After wounding, glial cells rapidly released the largest TNC isoform and proliferated in the border zones [10].
• Our results suggest that tenascin C is involved in the impaired mobility of OLG progenitor cells through increased amounts of adhesion complex as well as the prevention of wnt signaling [14].

Associations of Tnc with chemical compounds

• An angiotensin II receptor type 1 antagonist inhibited mechanical induction of brain natriuretic peptide but not tenascin-C [15].
• Antioxidants such as N-acetyl-L-cysteine, catalase, and 1, 2-dihydroxy-benzene-3,5-disulfonate significantly inhibited induction of tenascin-C [15].
• Selective depletion of this monocytic cell population, using either clodronate-liposomes or gadolinium chloride, prevented pulmonary adventitial remodeling (ie, production of collagen, fibronectin, and tenascin-C and accumulation of myofibroblasts) [16].
• Mechanical strain induced tenascin-C mRNA (3.9 +/- 0.5-fold, p < 0.01, n = 13) and tenascin-C protein in an amplitude-dependent manner but did not induce secreted protein acidic and rich in cysteine nor fibronectin [15].
• In experiments using various protein kinase inhibitors, we observed that selective inhibitors of cyclic GMP-dependent protein kinase, KT5823 and Rp-8-Br-cGMPS, blocked the effects of both the active sequence of thrombospondin 1 (hep I) and the alternatively-spliced segment (TNfnA-D) of tenascin-C on focal adhesion disassembly [17].

Physical interactions of Tnc

• Tenascin-C (TN-C) is a matrix molecule reported to bind some cell lines and to inhibit adhesion of some cell types to fibronectin [18].

Regulatory relationships of Tnc

• To investigate one aspect of the mechanisms, we focused on the role of tenascin C in regulating the migratory mobility of the progenitor cells via beta-catenin [14].
• Tenascin-C is a developmentally regulated extracellular matrix component [19].

Other interactions of Tnc

• Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed [20].
• Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue [13].
• The systemic BB-1101 injections also significantly reduced TN-C expression within the elastin implants [21].
• Cloning and sequence analysis of the PCR product indicated that SMCs express a Tn-C isoform with only repeats A1 and A2 of fibronectin type III repeats [11].
• Confocal microscopy at 8 days post injury revealed heightened immunoreactivity for phosphacan, NG2, and tenascin-C, particularly within fibronectin(+) scar tissue at lesion centers [13].

Analytical, diagnostic and therapeutic context of Tnc

• Quantitative Western blot analysis showed robust increases in neurocan, tenascin-C, and NG2 levels by 24 hr, suggesting that these molecules play a role in preventing axon regeneration across acutely forming scar tissue [13].
• We have used primers and RT-PCR to fully identify Tn-C isoforms expressed by SMCs [11].
• Balloon catheterization induces arterial expression of new Tenascin-C isoform [11].
• Using confocal Laser scanning microscopy, strong expression of tenascin-C and tenascin-X was found in the soft-diet group, mainly from the proliferative layer to the cartilage layer of the condyle, and posterior and anterior regions of the disk, in contrast to that of the control group, which was fed a hard diet [22].
• Arterial MMP-2 activity was measured by ELISA, whereas levels of tenascin-C and thrombospondin were assessed by Western blotting [23].

References