Disease relevance of TNNC1

• OBJECTIVE: To determine whether the extracellular matrix protein tenascin-C (TN-C) is overexpressed in lung fibroblasts from systemic sclerosis (SSc) patients, the molecular mechanisms regulating TN-C secretion in SSc and normal lung fibroblasts, and how these processes might contribute to lung fibrosis in SSc patients [1].
• These data suggest that TN-C reflects disease activity in cases of human myocarditis [2].
• Furthermore, serial biopsies from 22 patients were taken during convalescence, and sequential changes in TN-C levels were analysed [2].
• Here, we examined expression of TN-C variants and types of alternatively spliced fibronectin-type III (FNIII) repeats in chronic hepatitis [3].
• Both serum levels of IL-13 and the expression levels of TN-C in the dermis are increased in patients with systemic sclerosis [4].

High impact information on TNNC1

• In addition, cultured macrophages have the capacity to express the TN-C gene [5].
• To identify the cellular source of TN-C, the plaques were stained with smooth muscle cell- and macrophage-specific antibodies [5].
• In contrast, the inhibitory effect of TN-C on T lymphocyte activation remains unaffected [6].
• These three EBSs bind in vitro expressed Fli1 protein and mediate transactivation of the TN-C gene by Fli1 [7].
• To better understand the mechanisms that control TN-C gene expression, we examined the regulation of the human TN-C promoter in human fibroblasts [7].

Chemical compound and disease context of TNNC1

• Two patients treated with hyperthermia only had a slow increase in TN-C concentration peaking at day 4, while the patients treated with melphalan alone had no significant change [8].
• Tenascin-C (TN-C) is an extracellular matrix glycoprotein upregulated in various pathological processes [9].

Biological context of TNNC1

• Assignment of the human slow twitch skeletal muscle/cardiac troponin C gene (TNNC1) to human chromosome 3p21.3-->3p14.3 using somatic cell hybrids [10].
• The amino acid sequence of human cardiac troponin-C (TN-C) has been rabbit cardiac TN-C [11].
• The human TNNC1 locus had been assigned to a large region of chromosome 19, and we have refined the mapping position to the distal end of the chromosome by amplification of DNAs from a chromosome 19 mapping panel [12].
• Tenascin-C (TN-C), an extracellular matrix glycoprotein is expressed during embryonic development, but is present only at low levels in normal adult tissues [7].
• Tenascin-C (TN-C) is an extracellular matrix glycoprotein expressed along epithelial/stromal boundaries during tissue remodelling events, such as those that occur during morphogenesis, wound healing, and tumour invasion [13].

Anatomical context of TNNC1

• Consistent with the idea that thrombin is a physiologic inducer of TN-C, thrombin stimulated TN-C mRNA and protein expression in both SSc and normal lung fibroblasts by a mechanism that required proteolytic cleavage of the thrombin receptor [1].
• A tumour invasion model, in which established bladder cancer cell lines were seeded onto a normal bladder stroma, corroborated the evidence from the clinical specimens and demonstrated that TN-C was strongly expressed around foci of stromal invasion [13].
• TN-C was not expressed in neoplastic urothelium, although both TN-C and TGFbeta-1 may be involved in tissue remodelling during papillary tumour formation and invasion [13].
• Major TN-C variants in PBK-ABK corneas were in the range of 190 kDa to 240 kDa [14].
• Our findings suggest that astrocytes grown on TN-C revert to a quiescent, nonactivated state that is partially reversible [15].

Associations of TNNC1 with chemical compounds

• Significantly fewer astrocytes expressed scar properties when grown on tenascin-C (TN-C) than those cultured on other ECM proteins or poly-L-lysine-coated dishes [15].
• Integrin alphavbeta6 co-localized in the same area as TN-C and TN-C(L) immunoreactivity at the cell-cell contacts of the basal and suprabasal cell layers of the wound epithelium [16].
• By receiver-operating characteristic (ROC) analysis, TN-C levels clearly discriminated prediction of LV remodeling and MACE compared with other variables including plasma B-type natriuretic peptide, creatine kinase-MB, and LV function [17].

Analytical, diagnostic and therapeutic context of TNNC1

• PCR-based analysis of a 'monochromosomal' hybrid panel identified the presence of the TNNC1 gene on human chromosome 3 and subsequent analysis of the Genebridge4 radiation hybrid panel located the gene between D3S3118 (7.3cR) and GCT4B10 (4.2cR) with a lod score of > 3.0 [18].
• METHODS AND RESULTS: Immunohistochemical staining and in situ hybridization demonstrated minimal and random expression of TN-C in fibrotic but lipid-poor atherosclerotic plaques [5].
• A total of 113 biopsy specimens obtained from 32 patients with a clinical diagnosis of acute myocarditis were examined by immunohistochemistry and in situ hybridization for TN-C [2].
• Assessed by RT-PCR, PBK-ABK corneas expressed approximately three times more total TN-C mRNA than did normal corneas [14].
• Recently, TN-C-based radioimmunotherapy was administered to patients with GBM [19].

References