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Concept: Tenascin

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Recently, multiple culprits-in addition to melanocytes-have been implicated in the pathogenesis of vitiligo. Among those factors are fibroblasts. However, their exact role has not been clearly elucidated. The aim of the study was to evaluate the possible role played by fibroblasts in vitiligo via studying the expression Tenascin C and DKK1 in acral versus non-acral vitiligo lesions. This case-control study included 19 non-segmental vitiligo patients and ten controls. All patients were subjected to thorough clinical evaluation. Both Tenascin C and DKK1 were measured in lesional and peri-lesional skin of acral and non-acral lesions using ELISA technique. The measured levels of Tenascin C and DKK1 were significantly higher in the vitiligo group when compared to controls in all assessed sites (P < 0.05). Tenascin C was found to be significantly higher in lesional areas compared to peri-lesional ones only in the acral sites. DKK1 was significantly higher in lesional areas in all assessed sites (P < 0.05). The current work suggests a malfunction of fibroblasts in vitiligo, through demonstrating significant up-regulation of two melanogenesis inhibitory products (Tenascin C and DKK1) in patients compared to controls. Larger scale studies are warranted to detect the possible implications of such findings on vitiligo treatment.

Concepts: Epidemiology, ELISA, Study skills, Case-control study, Vitiligo, Tenascin, Tenascin C

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Platelet-derived biomaterials are widely explored as cost-effective sources of therapeutic factors, holding a strong potential for endogenous regenerative medicine. Particularly for tendon repair, treatment approaches that shift the injury environment are explored to accelerate tendon regeneration. Herein, genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of human-derived therapeutic factors in patch augmentation strategies aiming at tendon repair. Developed PL patches exhibited a controlled release profile of PL proteins, including bFGF and PDGF-BB. Additionally, PL patches exhibited an antibacterial effect by preventing the adhesion, proliferation and biofilm formation by S. aureus, a common pathogen in orthopaedic surgical site infections. Furthermore, these patches supported the activity of human tendon-derived cells (hTDCs). Cells were able to proliferate over time and an up-regulation of tenogenic genes (SCX, COL1A1 and TNC) was observed, suggesting that PL patches may modify the behavior of hTDCs. Accordingly, hTDCs deposited tendon-related extracellular matrix proteins, namely collagen type I and tenascin C. In summary, PL patches can act as a reservoir of biomolecules derived from PL and support the activity of native tendon cells, being proposed as bioinstructive patches for tendon regeneration.

Concepts: Bacteria, Collagen, Extracellular matrix, Cell biology, Tissue engineering, Tendon, Fibronectin, Tenascin

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Monocytes of patients with ankylosing spondylitis (AS) over-express toll-like receptor (TLR) 4. Tenascin-C (TNC) is an endogenous TLR4 ligand. Thus, we studied the serum and synovial fluid levels of TNC in AS. TNC was measured in serum of 36 AS patients (ASAS 2010 criteria) and 39 healthy controls by ELISA. Twenty-two patients were followed up after 3 months of standard treatment. Five paired serum-synovial fluid samples were also analyzed. Disease activity was assessed by BASDAI, ASDAS, swollen joint count, ESR, and CRP. All values are in median (IQR). Median age was 30 (20-35) years, and disease duration was 5.5 (1.3-10) years. Thirty-one were male. Twenty-five (69.5%) had peripheral arthritis. Median BASDAI was 5.3 (3.3-6.7). HLA B27 was positive in 34 (94.5%) cases. Median serum tenascin C levels were higher in AS [578.5 ng/ml] as compared to healthy controls [32.88 ng/ml, p < 0.0001]. Serum tenascin C levels correlated with ASDAS ESR [r = 0.367, p = 0.028] and ESR [r = 0.39, p = 0.035]. In patients with early disease (duration ≤ 5 years), serum levels had better correlation with ESR [r = 0.59, p = 0.009] and CRP [r = 0.479, p = 0.044]. On ROC analysis for active (PhGA ≥ 6) vs. inactive (PhGA ≤ 4) disease, tenascin-C (AUC = 0.60) performed as well as CRP (AUC = 0.65) and ESR (AUC = 0.73). Synovial fluid levels [11.61 (5.99-176.9) ng/ml] were lower than in serum [627.4 (488.5-779.1) ng/ml, p = 0.008]. Tenascin C fell levels with treatment [n = 11, 630.8 ng/ml to 376.4 ng/ml p = 0.0006] in treatment responders but not in non-responders [n = 11, 562.3 to 445.6, p = 0.33]. Serum TNC levels are raised in AS and may serve as marker of inflammation in early disease.

Concepts: Inflammation, Receptor, C-reactive protein, Ankylosing spondylitis, Reactive arthritis, HLA-B27, Tenascin, Tenascin C

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Tenascin C (TNC) is a key of extracellular matrix glycoprotein and highly express in numerous human malignancies. Herein, we attempted to clarify the clinicopathological significance of TNC as a prognostic determinant of breast ductal carcinoma. Then, we investigated TNC immunohistochemical expression in 150 breast ductal carcinomas and 27 normal breast tissue samples. Clinical relevance of TNC expression and the association TNC expression with other factors related to cancer-associated fibroblasts were also examined. In results, TNC expression was significantly higher in breast ductal carcinoma (56.0%) than normal breast tissues (25.9%). The upregulation TNC in cancer stromal were associated with pT stage (P=0.003), lymph node metastasis (P=0.002) and tumor node metastasis stage (P=0.001), also was correlated with an increase in tumor-associated macrophage population (P<0.001). The microvessel density (MVD) was significantly higher in TNC positive group than in negative group (P<0.001). In both univariate and multivariate Cox regression analyses, TNC was an independent poor prognostic factor for overall survival (OS) in breast ductal carcinoma patients. Importantly, over-expression TNC (P<0.001), FSP1 (P<0.001), SMA (P=0.002) and Vimentin (P=0.049) were significantly correlation with the lower OS (P<0.005). In addition, TNC expression in breast ductal carcinoma stromal was positively correlated with FSP1 (P<0.001), SMA (P=0.001) and Vimentin (P<0.001). In conclusion, the high expression of TNC could be a useful cancer-associated fibroblasts marker for the prediction of prognosis of breast ductal carcinoma patients.

Concepts: Cancer, Breast cancer, Metastasis, Lung cancer, Cancer staging, Extracellular matrix, Lymph node, Tenascin

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In breast cancer research S100A4-positive tumour-associated stromal cells are assumed as primary source of Tenascin C (TNC) in the metastatic environment. Aim of the present study was to isolate and characterize S100A4/TNC positive stromal canine mammary tumour (CMT) cells. Cells grown as scaffold-free spheroids were investigated for S100A4, TNC, and proliferative activity under 1.8% DMSO stimulation by means of Western blot and immunohistochemistry. DMSO is a commonly used drug solvent despite well-known side effects on cells including TNC expression. DMSO did not affect proliferation, but TNC was significantly reduced under DMSO exposure for 7 and 14 days, whereby for S100A4 a reducing effect was only observed after 14 days. Without DMSO, cells stably expressed TNC and S100A4 which makes them suitable to be used in experimental approaches requiring S100A4/TNC expressing CMT stromal cells. Results show that 1.8% DMSO should not be used as solvent for experiments concerning TNC/S100A4 expression.

Concepts: Gene expression, Cancer, Breast cancer, Metastasis, Breast, Expression, Mammary tumor, Tenascin

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To investigate the effect of Tenascin C (TNC) on the expression of pro-inflammatory cytokines and matrix metalloproteinases in human cardiac myofibroblasts (CMF).

Concepts: Hormone, Toll-like receptor, Tenascin

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The cellular mechanisms leading to infliximab therapy response in patients with ulcerative colitis (UC) are incompletely known. We therefore investigated early effects of infliximab therapy on monocytes and associated chemokines linked to clinical therapy response in UC patients.

Concepts: Immune system, Inflammation, Monocyte, Cell biology, Ulcerative colitis, Crohn's disease, Infliximab, Tenascin

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Acute aortic dissection (AAD) is caused by the disruption of intimomedial layer of the aortic walls, which is immediately life-threatening. Although recent studies indicate the importance of proinflammatory response in pathogenesis of AAD, the mechanism to keep the destructive inflammatory response in check is unknown. Here, we report that induction of tenascin-C (TNC) is a stress-evoked protective mechanism against the acute hemodynamic and humoral stress in aorta. Periaortic application of CaCl2 caused stiffening of abdominal aorta, which augmented the hemodynamic stress and TNC induction in suprarenal aorta by angiotensin II infusion. Deletion of Tnc gene rendered mice susceptible to AAD development upon the aortic stress, which was accompanied by impaired TGFβ signaling, insufficient induction of extracellular matrix proteins and exaggerated proinflammatory response. Thus, TNC works as a stress-evoked molecular damper to maintain the aortic integrity under the acute stress.

Concepts: Immune system, Inflammation, Extracellular matrix, Aortic dissection, Aorta, Acute accent, Fibronectin, Tenascin

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Purpose: Tenascin C (TNC) is a matricellular glycoprotein whose expression in adult tissue is indicative of tissue remodeling. The purpose of the current study was to determine the localization of TNC in trabecular meshwork ™ tissue and to analyze the effects of TNC on intraocular pressure (IOP). Methods: Human TM frontal sections were immunostained with anti-TNC and imaged by confocal microscopy. TNC mRNA and protein levels were quantitated in anterior segments perfused at physiological and elevated pressure. shRNA silencing lentivirus targeting full-length TNC (shTNC) was applied to anterior segment perfusion organ cultures. The IOPs and central corneal thickness (CCT) of wild-type, TNC (-/-) and tenascin X (TNX (-/-)) knockout mice were measured. Results: TNC was distributed in the juxtacanalicular (JCT) region of adult human TM, predominantly in the basement membrane underlying the inner wall of Schlemm’s canal. Application of shTNC lentivirus to human and porcine anterior segments in perfusion culture did not significantly affect outflow rate. Although TNC was up-regulated in response to pressure, there was no difference in outflow rate when shTNC-silenced anterior segments were subjected to elevated pressure. Furthermore, IOPs and CCTs were not significantly different between TNC (-/-) or TNX (-/-) and wild-type mice. Conclusions: TNC does not appear to contribute directly to outflow resistance. However, TNC immunolocalization in the JCT of adult human eyes suggests that certain areas of the TM are being continuously remodeled with or without an IOP increase.

Concepts: Eye, Intraocular pressure, Glaucoma, Part, Microscopy, Trabecular meshwork, Schlemm's canal, Tenascin