tenascin-C Levels Research Articles

Pankreas adenokarsinomunda serum tenascin-C düzeyi potansiyel bir biyobelirteç midir?

Objective: Tenascin-C (TNC) is an extracellular matrix protein involved in the tissue construction. Its expression levels have been detected low levels in normal tissues, but high in many tumors. In this study, we aimed to determine the clinical significance of serum TNC levels in patients with pancreatic adenocarcinoma (PA). Materials and Methods: Thirty-three patients with histopathologically confirmed PA diagnosis and sex- and age-matched 30 healthy controls were included into the current study. Serum TNC levels were measured using Enzyme-Linked Immuno Sorbent Assay (ELISA) method. Results: Median age was 59 (range, 32-84). Of the patients, 61% were male, 70% had good performance status, and 68% had tumors localized at pancreas head. Pancreaticoduodenectomy and palliative surgery were performed in 5 (15%) and 4 (12%) of the 9 (27%) patients who underwent surgical procedure. Serum TNC levels were found to be significantly higher in patients compared with control group (p0.05). Similarly, it was shown that serum TNC levels had no effect on overall survival (p=0.31). Conclusions: Serum TNC level is a diagnostic biomarker for patients with PA. However, it has neither predictive nor prognostic value in this group of patients.

Tenascin-C drives persistence of organ fibrosis.

The factors responsible for maintaining persistent organ fibrosis in systemic sclerosis (SSc) are not known but emerging evidence implicates toll-like receptors (TLRs) in the pathogenesis of SSc. Here we show the expression, mechanism of action and pathogenic role of endogenous TLR activators in skin from patients with SSc, skin fibroblasts, and in mouse models of organ fibrosis. Levels of tenascin-C are elevated in SSc skin biopsy samples, and serum and SSc fibroblasts, and in fibrotic skin tissues from mice. Exogenous tenascin-C stimulates collagen gene expression and myofibroblast transformation via TLR4 signalling. Mice lacking tenascin-C show attenuation of skin and lung fibrosis, and accelerated fibrosis resolution. These results identify tenascin-C as an endogenous danger signal that is upregulated in SSc and drives TLR4-dependent fibroblast activation, and by its persistence impedes fibrosis resolution. Disrupting this fibrosis amplification loop might be a viable strategy for the treatment of SSc.

Proteomic analysis of stromal proteins in different stages of colorectal cancer establishes Tenascin-C as a stromal biomarker for colorectal cancer metastasis.

Tumor microenvironment is crucial to tumor development and metastasis. Little is known about the roles of stromal proteins in colorectal carcinogenesis. In this study, we used a combination of laser capture microdissection (LCM), iTRAQ labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) to compare stromal proteomes in different stages of colorectal cancer. A total of 1966 proteins were identified, and 222 proteins presenting a significant fold change were quantified in different stages. Differentially expressed proteins (DEPs) were subjected to cluster and pathway analyses. We confirmed the differential expression of Tenascin-C and S100A9 using immunohistochemical analysis, and found that the expression levels of S100A9 and Tenascin-C were correlated with TNM stages and metastasis. In addition, our results showed that Tenascin-C was abundantly secreted by the colon cancer cells with high metastatic potential, and highly expressed in lymph nodes with metastasis. Our studies not only shed light on the mechanism by which stromal proteins contributed to colorectal carcinogenesis, but also identified Tenascin-C as a potential stromal biomarker for colorectal cancer metastasis.

Expression of the Extracellular Matrix Protein Tenascin-C Varies During Lactation.

Women diagnosed with pregnancy-associated breast cancer postpartum have a worse prognosis, stage for stage, than other women with breast cancer. The time of breast involution is tumor promotional. The extracellular matrix protein tenascin-C is upregulated during involution in animal models and promotes breast cancer progression. It interacts with transforming growth factor (TGF)β, which also is involved in breast involution and breast cancer progression. Little is known about the expression of tenascin-C during human breast involution, nor its relationship to TGFβ. The purpose of this study was to investigate the expression of tenascin-C throughout lactation, as well as its relationship to TGFβ1 and TGFβ2. Three milk samples from 25 lactating women (transitional, whole, and wean) were collected, separated into components (cells, fat, and skim), and the skim fraction analyzed for total protein, tenascin-C, TGFβ1, and TGFβ2. Tenascin-C, TGFβ1, and TGFβ2 were detectable in all milk samples. Highest tenascin-C levels on average were found in whole milk, whereas highest mean TGFβ1 and TGFβ2 levels were in wean milk. Wean samples on average had higher levels of both TGFβ1 (26%) and TGFβ2 (>500%) than matched transitional milk samples. Tenascin-C levels in wean milk were associated with nursing length (p = 0.048). Combining all three milk collection time points, tenascin-C exhibited a weak inverse correlation with TGFβ1 and TGFβ2 (p < 0.1). The inverse correlation at the wean time point was stronger for TGFβ2 than -1 (-0.37 versus -0.25). Tenascin-C, a protein known to promote breast cancer progression, is expressed throughout lactation. The inverse correlation with TGFβ2 in wean milk suggests a possible interaction during breast involution, which should be further investigated.

Inflammatory markers and circulating extracellular matrix proteins in patients with chronic obstructive pulmonary disease and left ventricular diastolic dysfunction.

Left ventricular diastolic dysfunction (LVDD) is a frequent condition in chronic obstructive pulmonary disease (COPD). Tenascin-C (Tn-C) and matrix metalloproteinase-9 (MMP-9) are extracellular matrix proteins associated with myocardial fibrosis and wall remodeling because of inflammation. To determine whether the circulating levels of inflammatory markers, Tn-C and MMP-9 are associated with LVDD in COPD patients. Forty-two severe stable COPD patients (64 ± 8 years, 88% male, FEV1% 38 ± 5.7) and a control group (n = 11) were included. Pulmonary function tests and a Doppler echocardiography were performed on COPD patients. Baseline serum levels of C-reactive protein (CRP), leukocytes, fibrinogen, interleukins (IL) 6 and 8, Tn-C and MMP-9 were analyzed in all participants. COPD patients were classified in two groups: LVDD (n = 35) and non-LVDD (n = 7). Serum levels of IL-6 and CRP were higher in the LVDD group compared to the non-LVDD group [median(IQR)] [3.46 pg/mL (2.36-4.74) vs 1.87 pg/mL (1.10-3.28), P = 0.045] and [6.0 mg/L (3.0-13.0) vs 1.0 mg/L (1.0-2.3), P = 0.001], respectively. The same trend was observed in the analysis adjusted by age and BMI, being significant for CRP (P = 0.04). Circulating IL-6 was associated with the type of LVDD, being higher in the type-II (P = 0.046). Obese patients with COPD-LVDD showed a higher level of inflammatory markers (P = 0.021). Tn-C were significantly higher in patients with LVDD type-II compared to type-I [1422 ng/mL (826-1948) vs 781 ng/mL (640-1139), P = 0.015], without differences in MMP-9. Severe COPD patients with LVDD showed a different inflammatory pattern, suggesting a link between low-grade inflammation and the presence of LVDD. In COPD, high levels of Tn-C are related to LVDD type-II.

Role of Tenascin-C as a Predictor of Left Ventricular Remodeling after Streptokinase in Patients with Acute Myocardial Infarction

We investigated clinical implications of serum tenascin-C (TN-C) levels in patients with acute myocardial infarction (AMI) treated with thrombolytic therapy Serum TN-C levels were measured by ELISA in 60 cases presented with acute STEMI and 20 normal controls. The mean serum TN-C level of AMI patients on admission (57.5 ng/ml) was significantly higher than that of controls (57.49 ± 19.89 ng/ml vs. 34 ± 3.02 ng/ml; p=0.0001), follow-up examination (mean: 6 months) revealed that 17 of 60 AMI (28%) patients showed left ventricular (LV) remodeling (20% end-diastolic volume increase), and in 6 (10%), major adverse cardiac events (MACE) were detected. By receiver-operating characteristic (ROC) analysis, TN-C levels clearly discriminated prediction of LV remodeling and MACE compared with other variables including creatine kinase-MB, and LV function. Diabetes and TN-C were correlated with MACE in our study. The findings suggest that serum TN-C levels might be useful in predicting LV remodeling and prognosis after AMI.

Tenascin C affects mineralization of SaOS2 osteoblast-like cells through matrix vesicles

Tenascin C (TNC) is an extracellular matrix glycoprotein involved in osteogenesis and bone mineralization. In a previous study, we identified TNC protein located in the matrix vesicles (MVs) of osteoblasts. MVs are determinant in the mineralization formation. Therefore, we hypothesize whether TNC can modulate osteoblast mineralization via MVs. In this study, we demonstrated that the expression level of TNC was increased with osteoblast differentiation of osteoblast-like SaOS2 cells, and down-regulation of TNC expression by siRNA could significantly inhibit SaOS2 differentiation toward osteoblasts and mineralization as evidenced by decreases in ALP activity, mineralized nodule formation, calcium deposition, and down-regulation of osteogenic marker genes ALP, and COL1A1. Furthermore, we validated that TNC located in the MVs of mineralized SaOS2 cells, and that down-regulation of TNC could decrease MVs mineralization ability in vitro, and the decrease of MVs mineralization ability was not associated with annexins. In conclusion, in this study, we extended the role of TNC during osteogenesis previous progresses, and that supported TNC as an important functional MVs component in modulating osteoblast mineralization.

Tenascin- C: A Promising Marker in Identifying Patients with Cardiovascular and Pulmonary Remodeling

Objectives: Our aim was to study serum levels of tenascin-C (TnC ) in patients with pulmonary hypertension and left ventricular hypertrophy in order to explore its diagnostic utility for cardiac remodeling among elderly patients admitted at Ain Shams University hospitals, Egypt. Methods: A case control study was conducted on 279 elderly selected from Ain Shams University Hospital. They were classified into 3groups; (Group I): 105 cases suffering from pulmonary hypertension (PH), (Group II):114 cases suffering from systemic hypertension and (Group III): 60 apparently healthy subjects serving as control group. Group I was classified according to WHO classification into 4 classes. Group I was reclassified according to the disease severity into 2 subgroups. Group II was reclassified into 2 subgroups according to presence or absence of concomitant left ventricular hypertrophy (LVH). All subjects were subjected to history taking, clinical examination, echocardiograhic measurements (for cases only), TnC assay by enzyme linked immunosorbent assay (ELISA) and lipid profile. Results: Serum tenascin-C showed a highly significant elevation in PH and LVH cases than controls (p<0.001). In addition, (ROC) curve analysis revealed a superior performance of TnC in discrimination of PH cases from healthy controls at cut-off value of 0.3ng/mL with sensitivity (91.4%), specificity (100%). Moreover, the diagnostic performance of TnC in discriminating PH patient’s subgroups was best at cut-off value of 4.3ng/mL with sensitivity (89.3%), specificity (85.7%).Conclusion: Serum TnC is a promising diagnostic marker for identifying patients with tissue remodeling in PH and LVH.

Relation between coronary artery calcium score and serum tenascin-C level in patients without known coronary artery disease

Objective Presence of coronary artery disease (CAD) also in subjects without traditional risk factors leads to a search for new risk factors. Tenascin-C (TNC), an extracellular matrix glycoprotein is normally found in very low concentrations in tissues and serum of adults, whereas its expression is enhanced in case of pathological conditions accompanied by inflammation. This study aimed to investigate the relation between coronary artery calcium score (CACS) and serum TNC level.Methods Ninety patients (age range, 18-75 years) presenting with chest pain but without known CAD were divided according to their CACSs as control (CACS = O, n = 30), low CACS (CACS between 0 and 400, n = 30), and high CACS (CACS ≥ 400, n = 30) groups. The patients were questioned about risk factors and underwent laboratory analyses for biochemical parameters including TNC.Results The mean TNC level was significantly higher in the high CACS group as compared to both the low CACS group and the control group [4.7 (0.03-30.7), 28 (0.7-212) and 84 (2-456) ng/mL, respectively; P < 0.01]. A positive correlation was determined between serum TNC level and CACS (r = 0.641, P < 0.001). In the ROC curve analysis, when the cut-off value for TNC was accepted as 8.09 ng/mL, the sensitivity and specificity in detecting patients with CACS > 100 (moderate or significant calcification) were 72% and 82%, respectively.Conclusion A significant relationship was found between CACS and serum TNC level. Thus, measurement of TNC level can be used in determining elevated CACS and thereby the risk for CAD.

Serum tenascin-C discriminates patients with active SLE from inactive patients and healthy controls and predicts the need to escalate immunosuppressive therapy: a cohort study.

IntroductionThe aim of this study was to examine whether circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) are useful as an activity-specific or predictive biomarker in systemic lupus erythematosus (SLE).MethodsSerum TNC levels were determined by enzyme-linked immunosorbent assay at inception visit in a prospective cohort of 59 SLE patients, and in 65 healthy controls (HC). SLE patients were followed for a mean of 11 months, disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3–6 months, and changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially. We examined cross-sectionally the relationships between serum concentrations of TNC and SLE status, SLEDAI-2 K scores, strata of disease activity, and levels of conventional biomarkers [anti–double-stranded DNA (dsDNA), anti-nucleosome antibodies, C3 and C4]. We also explored the utility of TNC levels for predicting disease flares, defined as (i) new/increased GC, (ii) new/increased GC or IS, and (iii) increase in SLEDAI by ≥3 or (iv) BILAG A or B flare.ResultsThere was no significant difference in the mean levels of TNC between the SLE patients and HC. However, in SLE patients with active disease (SLEDAI ≥6), the TNC levels were significantly higher than in the HC (p = 0.004) or in patients with no/low disease activity (p = 0.004). In SLE patients, TNC levels were significantly associated with positivity of anti-dsDNA (p = 0.03) and anti-nucleosome antibodies (p = 0.008). Flares defined by a need to escalate immunosuppressive therapy were captured more frequently and earlier than flares defined by standard activity indices. Higher baseline levels of serum TNC presented a significantly greater risk of flare (i) [hazard ratio (HR) 1.39, 95 % confidence interval (CI) 1.11–1.73] or (ii) (HR 1.25, 95 % CI 1.02–1.52) but not of flares (iii) or (iv). The baseline serum TNC level was the single most important independent predictor of flare (i) compared with conventional biomarkers.ConclusionsTNC is not disease-specific, but it seems to indicate the activity of SLE and may predict the need to escalate immunosuppressive therapy. TNC levels may thus serve as a useful activity-specific and predictive biomarker in SLE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0862-4) contains supplementary material, which is available to authorized users.

ACE inhibition modifies exercise-induced pro-angiogenic and mitochondrial gene transcript expression.

Skeletal muscle responds to endurance exercise with an improvement of biochemical pathways that support substrate supply and oxygen-dependent metabolism. This is reflected by enhanced expression of associated factors after exercise and is specifically modulated by tissue perfusion and oxygenation. We hypothesized that transcript expression of pro-angiogenic factors (VEGF, tenascin-C, Angpt1, Angpt1R) and oxygen metabolism (COX4I1, COX4I2, HIF-1α) in human muscle after an endurance stimulus depends on vasoconstriction, and would be modulated through angiotensin-converting enzyme inhibition by intake of lisinopril. Fourteen non-specifically trained, male Caucasians subjects, carried out a single bout of standardized one-legged bicycle exercise. Seven of the participants consumed lisinopril in the 3 days before exercise. Biopsies were collected pre- and 3 h post-exercise from the m. vastus lateralis. COX4I1 (P = 0.03), COX4I2 (P = 0.04) mRNA and HIF-1α (P = 0.05) mRNA and protein levels (P = 0.01) showed an exercise-induced increase in the group not consuming the ACE inhibitor. Conversely, there was a specific exercise-induced increase in VEGF transcript (P = 0.04) and protein levels (P = 0.03) and a trend for increased tenascin-c transcript levels (P = 0.09) for subjects consuming lisinopril. The observations indicate that exercise-induced expression of transcripts involved in angiogenesis and mitochondrial energy metabolism are to some extent regulated via a hypoxia-related ACE-dependent mechanism.

A new predictor of mortality in hemodialysis patients; Tenascin-C.

Cardiovascular disease is the most frequent cause of mortality in hemodialysis patients. There are a number of inconsistencies in terms of cardiovascular risk factors in these patients. Tenascin C (TN-C) is a matricellular protein which may be a prognostic predictor after myocardial infarction and many cardiac diseases. The purpose of this study was to determine TN-C levels in hemodialysis patients and to evaluate the association between TN-C levels and cardiac mortality. In this multicenter prospective observational research, blood specimens were collected at the start of the study for the measurement of TN-C and other biochemical parameters. After 2 years' follow-up we investigated the association between TN-C and other biochemical and demographic parameters and cardiac and all cause mortality. Two hundred thirty-eight patients and 25 healthy individuals were enrolled. TN-C levels in the hemodialysis group were higher than those in the control group (p b 0.001). All-cause mortality was observed in 47 (19%) patients and cardiac mortality in 39 (15%). At multivariate Cox regression analysis, TN-C, age and systolic blood pressure were identified as independent predictors of cardiac mortality. The Kaplan–Meier survival curve revealed greater all-cause and cardiac mortality rates in the high TN-C group (Log rank p b 0.001 and p b 0.05 respectively). TN-C levels were higher than those in the control group, and our results suggest that it may be a predictor of cardiac mortality in hemodialysis patients. If further studies support our research, TN-C may be a useful biomarker for detecting cardiac mortality risk.

A new player in chronic kidney disease mineral and bone disorder: tenascin-C.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a condition frequently observed in CKD. The search for a reliable and easy to use biomarker in the diagnosis of CKD-MBD is continuing. Tenascin-C (TN-C) is an important extracellular (ECM) protein synthesized by osteoblasts during bone growth and morphogenesis. The purpose of this study was to assess the relation between inflammation and MBD and TN-C in HD patients and to identify a new marker that can be used to help diagnose CKD-MBD. 136 HD patients and 22 healthy controls were enrolled in this cross-sectional, observational multicenter study. Once patients' demographic and biochemical parameters had been recorded, peripheral blood samples were collected for TN-C measurement before the mid-week HD session. The relationship between TN-C levels and demographic and biochemical parameters was then assessed. TN-C levels were significantly higher in the HD patient than in the control group (P&lt;.001). Intact parathormone (iPTH) affected TN-C levels in the HD patient group. TN-C levels was significantly higher in both the high (&gt;300 pg/ml) and low iPTH groups (&lt;150 pg/ml) compared to the 150-300 pg/ml iPTH group (P&lt;.001, &lt;.001 respectively). This study showed, for the first time in the literature, high levels of TN-C in the low and high iPTH groups and that this elevation was associated with iPTH. We think that if our study is supported by further research, TN-C can be a biomarker capable of use in diagnosing CKD-MBD.

Abstract O.31: Tenascin-C can be a Novel Prognostic Biomarker For Kawasaki Disease

Tenascin-C (TNC) is an extracellular matrix glycoprotein sparsely detected in normal but highly expressed in pathological condition associated with inflammation in variety of tissues. By taking advantage of its specific expression, TNC is applicable as a biomarker and a molecular imaging target for diagnosis of disease activity for ventricular remodeling. In blood vessels, the expression of TNC in normal is generally low but strong expression is linked with several pathological conditions such as pulmonary artery hypertension, coronary atherosclerotic intima, and aortic aneurysm/ dissection. We hypothesized that TNC could be useful for evaluating disease activity of Kawasaki Disease(KD). We measured serum level of TNC of 174 patients with KD using ELSA and found that the TNC level was significantly higher than that of the controls, and the initial treatment with intravenous immunoglobulin decreased the level. Combination of serum TNC and Kobayashi score increased the accuracy to identify cases at a high risk of unresponsiveness to high-dose intravenous immunoglobulin. Immunohistochemical analysis of autopsied cases showed that TNC was strongly expressed in coronary vascular lesion at acute stage of KD patients as well as in the Candida albicans-induced murine model of vasculitis/aneurysm. Biomechanical analysis demonstrated that vascular flexibility was reduced in TNC knockout mice. A combination of inflammation and mechanical stress to aorta induced dissecting aneurysm in TNC knockout mice. In vitro, TNC enhanced macrophage migration and cytokine synthesis, meanwhile TNC synthesis was up-regulated by various pro-inflammatory cytokines. These results suggest that TNC is expressed in vascular lesion of KD reflecting active inflammation, which has diverse functions to modulate not only inflammatory response but also regulate vascular remodeling and aneurysm formation. TNC could be a key molecule in pathophysiology and a promising biomarker of KD.

Abstract 98: Tenascin-C as a Novel Biomarker for Predicting Therapeutic Effect in Kawasaki Disease

Background: In acute stage of Kawasaki disease (KD), patients who are unresponsive to initial therapy are immediately administered additional therapy to prevent the development of coronary artery abnormalities (CAAs). Although failure to respond is defined as persistent or recrudescent fever after treatment, it is difficult to recognize the presence of fever because steroids are administered with intravenous immunoglobulin (IVIG) in severe KD patients in Japan. In addition, inflammatory markers such as CRP usually decrease after initial therapy in patients who are unresponsive to initial therapy and there is no biomarker for monitoring treatment effect. Tenascin-C (TN-C) is an extracellular matrix protein specifically upregulated in response to tissue injury and inflammation. Methods: We recruited 174 patients (male 102, female 72) from August 2011 to April 2014, from fourteen institutions in Japan. Serum levels of TN-C (sTN-C) were examined using ELISA before and after initial treatment. The initial treatments consisted of: 30 aspirin only, 111 IVIG + aspirin, and 33 IVIG + aspirin + prednisolone. We compared patients who responded to initial therapy (R group; n = 134) with those who did not respond (NR group; n = 40) regarding patient profile and laboratory data. Results: Patients in NR group had higher % neutrophil (p = 0.004), CRP (p = 0.012) and sTN-C (p = 0.049) than in R group before treatment. After initial therapy, WBC, % neutrophil and CRP significantly decreased in both groups (p &lt; 0.001), but sTN-C did not significantly decrease in NR group (p = 0.485). When sTN-C after initial therapy was used to predict unresponsiveness of initial therapy, sensitivity, specificity and AUC were 85%, 55%, and 0.745 respectively. Especially in patients who were administered steroids with IVIG as initial therapy, the accuracy of predictive model using sTN-C after initial therapy was high (AUC 0.812, sensitivity 71%, specificity 81%). The incidence of CAAs tends to be higher in NR group than in R group (12.5 vs. 3.7 %, p = 0.051). Conclusions: TN-C is a potential biomarker in predicting the need for additional therapy. Especially in KD patients who are treated by steroids with IVIG, TN-C may be useful.

Tenascin-C Levels, A Toll-like Receptor 4 Ligand, in Enthesitis-related Arthritis Category of Juvenile Idiopathic Arthritis: A Cross-sectional and Longitudinal Study.

Monocytes of children with enthesitis-related arthritis (ERA) show Toll-like receptor 4 (TLR4) overexpression. Tenascin-C (TNC) is an extracellular matrix glycoprotein and acts as an endogenous TLR4 ligand. Thus, we studied the serum and synovial fluid (SF) levels of TNC in children with ERA. TNC was measured in the serum of 80 children with ERA satisfying the International League of Associations for Rheumatology criteria. Fifteen children were followed up while being treated with regular nonsteroidal antiinflammatory drug (NSAID) therapy and levels were reassessed at 3 months. Seventeen paired serum-SF samples and 25 healthy control serum samples were also analyzed. Disease activity was assessed by physician's global assessment (PGA), early morning stiffness (EMS), tender (TJC) and swollen joint counts (SJC), enthesitis score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The mean serum TNC level in patients with active disease (67.1 ± 44.9 ng/ml) was significantly higher than in those with inactive disease (40.6 ± 36.7 ng/ml, p = 0.01) and healthy controls (21 ± 15.2 ng/ml, p < 0.001). Levels of TNC were higher in HLA-B27-positive (58.4 ng/ml) versus -negative disease (20.4 ng/ml, p = 0.01). TNC levels correlated moderately with disease activity: PGA r = 0.4, EMS r = 0.34, TJC r = 0.4, SJC r = 0.46, ESR r = 0.42, and CRP r = 0.32. In receiver-operation characteristic analysis for active versus inactive diseases, TNC [area under the curve (AUC) = 0.754] was equivalent to ESR (AUC = 0.787) and CRP (AUC = 0.789). Regular NSAID therapy led to a significant fall in serum TNC levels at 3 months (p = 0.0003). The SF TNC level was 17.39 ng/ml, significantly lower than the paired serum values (p = 0.01). Serum TNC levels are significantly raised and correlate with various clinical and laboratory variables of disease activity in children with ERA. Regular NSAID therapy reduces the TNC levels, probably related to controlling disease activity.

Tenascin C levels in patients with mild and severe preeclampsia

Objective: To determine the serum tenascin-C (TN-C) levels in cases with mild and severe preeclampsia.Methods: Pregnant women were divided into three groups, namely healthy pregnants (Group 1, n = 20), pregnants with mild preeclampsia (Group 2, n = 20) and pregnants with severe preeclampsia (Group 3, n = 20). The groups were formed so as to match each other in terms of gestational week. From each pregnant woman, pre- and post-delivery blood samples were obtained to measure serum TN-C levels. The data were evaluated using the Kruskall–Wallis variance analysis. For the obtained values of p < 0.05, the groups were compared in pairs. A p value of < 0.017 was accepted as significant.Results: In Groups 1, 2 and 3, the prepartum TN-C levels were 5.02 ± 0.4 µg/ml, 12.8 ± 2.9 µg/ml and 33.8 ± 11.7 µg/ml, and in the postpartum TN-C levels were 4.7 ± 0.1 µg/ml, 11.7 ± 1.8 µg/ml and 50.6 ± 33.8 µg/ml, respectively. There was a significant difference between the groups in terms of the prepartum and postpartum TN-C levels (p < 0.017, Mann–Whitney U [MWU] test). There was also a significant difference in the prepartum TN-C levels between Groups 2 and 3 (p < 0.017, MWU test).Conclusions: The prepartum and postpartum TN-C levels were significantly higher in mild and severe preeclampsia than those in healthy pregnants.

Effluent Tenascin-C Levels Reflect Peritoneal Deterioration in Peritoneal Dialysis: MAJOR IN PD Study

Peritoneal deterioration causing structural changes and functional decline is a major complication of peritoneal dialysis (PD). The aim of this study was to explore effluent biomarkers reflecting peritoneal deterioration. In an animal study, rats were intraperitoneally administered with PD fluids adding 20 mM methylglyoxal (MGO) or 20 mM formaldehyde (FA) every day for 21 days. In the MGO-treated rats, tenascin-C (TN-C) levels in the peritoneal effluents were remarkably high and a cluster of TN-C-positive mesothelial cells with epithelial-to-mesenchymal transition- (EMT-) like change excessively proliferated at the peritoneal surface, but not in the FA-treated rats. Effluent matrix metalloproteinase-2 (MMP-2) levels increased in both the MGO- and FA-treated rats. In a clinical study at 18 centers between 2006 and 2013, effluent TN-C and MMP-2 levels were quantified in 182 PD patients with end-stage renal disease. Peritoneal function was estimated using the peritoneal equilibration test (PET). From the PET results, the D/P Cr ratio was correlated with effluent levels of TN-C (ρ = 0.57, p < 0.001) and MMP-2 (ρ = 0.73, p < 0.001). We suggest that TN-C in the effluents may be a diagnostic marker for peritoneal deterioration with EMT-like change in mesothelial cells in PD.

The correlation between tenascin-C expression, and formation of intestinal stricture.

OBJECTIVE:A strong correlation exists between tenascin-C induction, and acute inflammation. Generally increased tenascin-C concentrations are correlated with various inflammatory, and infectious diseases. In patients with diagnosis of Inflammatory Bowel Disease (IBD) presence of tenascin-C in colonic mucosa demonstrates tissue repair, and its mucosal concentrations are correlated with local disease activity Therefore plasma levels of tenascin-C have been demonstrated to be a helpful indicator of the activity of inflammatory bowel diseases. In this study, firstly in the literature, we aimed to display the correlation between tenascin-C expression, and formation of intestinal stricture.METHODS:A total of 43 patients (male, n=19; 44.2%; and female, n=24, 55.8%) aged between 19, and 63 years, with clinically, endoscopically, radiologically, and histopathologically confirmed definitive diagnosis of Crohn’s disease who were examined, diagnosed, and treated in the Gastroenterology Clinic of Haydarpasa Numune Training and Research Hospital between January 2011, and April 2012 were investigated. Serum tenascin-C levels were measured using commercial sandwich enzyme-linked immunosorbent assay Human Tenascin-C Purified Protein kit (Chemicon, Millipore(R), USA). Study groups were categorized based on the type of the disease as inflammatory (n=17; 39.5%), obstructive (27.2%), and fistule formation (n=10; 23.3%) Crohn’s disease. For statistical analysis SPSS (Statistical Package for Social Sciences) Statistics 15 program was used.RESULTS:Median tenascin- C value in the obstructive group (6.57 ng/mL; range, 4.26-21.87 ng/mL) was statistically significantly higher than that detected in the inflammatory (1.74 ng/mL; range,1.29-3.16 ng/mL), and fistulizing (1.44 ng/mL; range, 0.74-2.47 ng/mL) groups (p=0.002).CONCLUSION:Intestinal fibroblasts have an important role in the stricture formation process in CD. Transforming growth factor (TGF)-b1 cytokine is in the center of this process. A strong correlation exists between tenascin-C induction, and acute inflammation. As a known fact, serum tenascin-C levels can be used in the determination of activity of IBD. Starting from this point, serum tenascin-C levels can be useful in the categorization of the Crohn’s disease without the need for invasive methods. In the future, studies with larger patient series investigating use of serum tenascin-C in the prediction of stricturing Crohn’s disease should be conducted.

Abstract 15745: Tenascin-c Levels and Clinical Importance in Pulmonary Arterial Hypertension

Background: Prognostic markers are known to have an important value in guiding treatment of pulmonary arterial hypertension (PAH) which is associated with high mortality and morbidity. The prognostic importance of some biomarkers like BNP has been shown and used in the routine course of PAH. Tenacsin-C (TNC) is a glycoprotein located in the extracellular matrix which has an important role in PAH pathophysiology. However, the clinical relevance of PAH and TNC is unknown. In this study, we investigated the plasma levels of TNC in patients with PAH as a possible prognostic marker. Methods: Study population consisted of 45 PAH (29 women, mean age: 32±9 years, 34 with PAH associated with congenital heart disease, 9 idiopathic PAH and 2 chronic thromboembolic pulmonary hypertension) patients who were followed-up in our PAH centre. Twenty age-sex matched healthy subjects served as the control-group. Plasma TNC levels were measured using ELISA-method. All patients were evaluated with transthoracic echocardiography including assessment of right ventricle, six minute walk test, and NT-proBNP levels simultaneously, which are all known to have prognostic value in PAH. Data were comparatively evaluated using appropriate statistical analysis. Results: TNC levels in patients with PAH were significantly higher, compared to healthy controls (61.9±20.7 ng/mL versus 12.6±5.6 ng/mL, respectively, p&lt;0.0001). There was no significant relationship between age, gender, and TNC levels. There was a significant positive correlation between TNC levels in PAH group and functional class (rho=0.355, p=0.017) and NT-proBNP (rho=0.5, p=0.001) levels, whereas there was a significant negative correlation between TNC levels and fractional area change (FAC, rho=-0.33, p=0.035) and tricuspid annular plane systolic excursion (TAPSE, rho=-0.495, p=0.006). Conclusions: TNC levels are substantially increased in PAH. There is a significant association between TNC levels and parameters with proved prognostic value in PAH, such as functional class, TAPSE, FAC, and NT-proBNP levels. All of these data suggest that TNC levels in patients with PAH may be a new prognostic biomarker. Further prospective studies are needed to confirm this statement.