Tenascin Research Articles

Bridging the Diagnostic Gap for Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders: Evidence of a Common Extracellular Matrix Fragmentation Pattern in Patient Plasma as a PotentialBiomarker.

Diagnosing hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD), common overlapping multisystemic conditions featuring symptomatic joint hypermobility, is challenging due to lack of established causes and diagnostic tools. Currently, the 2017 diagnostic criteria for hEDS are used, with non-qualifying cases classified as HSD, although the distinction remains debated. We previously showed extracellular matrix (ECM) disorganization in both hEDS and HSD dermal fibroblasts involving fibronectin (FN), type I collagen (COLLI), and tenascin (TN), with matrix metalloproteinase-generated fragments in conditioned media. Here, we investigated these fragments in patient plasma using Western blotting across diverse cohorts, including patients with hEDS, HSD, classical EDS (cEDS), vascular EDS (vEDS), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and healthy donors, uncovering distinctive patterns. Notably, hEDS/HSD displayed a shared FN and COLLI fragment signature, supporting their classification as a single disorder and prompting reconsideration of the hEDS criteria. Our results hold the promise for the first blood test for diagnosing hEDS/HSD, present insights into the pathomechanisms, and open the door for therapeutic trials focused on restoring ECM homeostasis using an objective marker. Additionally, our findings offer potential biomarkers also for OA, RA, and PsA, advancing diagnostic and therapeutic strategies in these prevalent joint diseases.

Tenascin can inhibit apoptosis induced by copper in silver pomfret (Pampus argenteus)

Silver pomfret, an economically important fish species, encounters significant challenges posed by copper pollution in wild and culturing environment. High level of copper has the potential to accumulate in aquatic organisms over prolonged exposure periods. The extracellular matrix, which is highly susceptible to copper, encompasses various proteins, among which tenascin (TN) might play a crucial role in potentially regulating copper-induced apoptosis. To investigate this hypothesis in fish, we initially identified six TN family members in silver pomfret, namely TNCa, TNCb, TNR, TNXB, TNXBa and TNN. Phylogenetic analysis showed four gene subfamilies, namely TNC, TNR, TNN, and TNX, through comparative analysis with TNs from seven other teleost fish species. Subsequently, we analyzed transcriptome of silver pomfret under copper stress and found differential expression of TN family genes under varying levels of copper stress, particularly TNCa. KEGG enrichment analysis demonstrated a significant enrichment of TN downstream pathway, specifically the Pi3K-AKT signaling pathway. RT-qPCR results indicated up-regulation of TNs and apoptosis inhibition-related genes and down-regulation of apoptosis promotion-related genes within this pathway. Hence, we speculated that TN inhibits copper-induced apoptosis by modulating this particular pathway. To further validate this hypothesis, we established a copper stress cell model using a silver pomfret kidney cell line (PaK) and utilized siRNA to knock down TNCa expression within this cellular model. Comparing RNAi-Cu group to NC-control group, we observed significantly reduced cell viability and intensified apoptosis signals in the former. Additionally, RNAi-Cu group displayed down-regulation of apoptosis inhibition-related genes and up-regulation of apoptosis-related genes in Pi3K-AKT signaling pathway compared to NC-Cu group. These findings indicated that TN might be able to inhibit copper-induced apoptosis through Pi3K-AKT signaling pathway. Ultimately, this study offers foundational knowledge for exploring heavy metal toxicity effect on fishes and some references for utilization of copper in parasite control.

The Regulation of the Function of Fibroblasts in Patients with Chronic Obstructive Pulmonary Disease by Regulating Tenascin-C Protein Under Feedback Lung Training with Curcumin in Combination with Suzi Jiangqi Decoction

Chronic obstructive pulmonary disease (COPD) is characterized by reduction of elastic fibers in alveolar wall. This study explores the mechanism of curcumin combined with Suzi Jiangqi Decoction in lung fibroblasts. 50 COPD patients suspected of lung cancer were collected. Ten patients were assigned into control group, and the remaining 40 patients underwent feedback lung training and were divided into model group, curcumin group, Suzi Jiangqi decoction group, and curcumin combined with Suzi Jiangqi decoction group. 5 mL peripheral venous blood was collected and a percutaneous lung biopsy was performed to collect lung tissue and culture fibroblasts. Tenascin (TNC) level was detected by ELISA and pathological changes of lung tissue were detected by HE staining. CCK-8 assay detected cell proliferation and Transwell chamber detected cell migration. Cell apoptosis was assessed by flow cytometry and TGF-β1, MMP-9, and TNC expression were evaluated by Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot. TNC level in COPD patients decreased significantly and levels of various pulmonary function indexes showed an upward trend. The epithelial cells in lung tissue of control group were less and alveolar wall was obviously thinner. Epithelial cells gradually increased and alveolar walls gradually fused. TNC protein can improve the development of fibroblasts in COPD patients. Curcumin combined with Suzi Jiangqi Decoction inhibited TNC expression, and down-regulated TGF-β1 and MMP-9. Curcumin combined with Suzi Jiangqi decoction increased the proliferation ability and reduced apoptosis of lung fibroblasts by down-regulating the expression of Tenascin-C. This study provides a solid theoretical basis for curcumin combined with Suzi Jiangqi Decoction as a treatment for COPD.

Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids

Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.

Protein Biomarkers and Major Cardiovascular Events in Older People With Advanced CKD: The European Quality (EQUAL) Study

Rationale & ObjectiveCardiovascular disease is the leading cause of morbidity and mortality in chronic kidney disease (CKD). We investigated 184 inflammatory and cardiovascular proteins to determine their potential as biomarkers for major cardiovascular events (MACE). Study DesignEQUAL is an observational cohort study which enrolled people aged ≥65 years with an estimated glomerular filtration rate ≤20 ml/min/1.73m2. Setting & ParticipantsRecruited participants were split into Discovery (n=611) and Replication cohorts (n=292). ExposureOne hundred and eighty four blood protein levels measured at the baseline visit, each protein was analysed individually. OutcomeMACE. Analytical ApproachCox proportional hazard models adjusted for age, sex, eGFR, previous MACE and country were used to determine the risk of MACE. Proteins with false discovery rate adjusted P values <0.05 in the Discovery cohort were tested in the Replication cohort. Sensitivity analyses were performed, adjusting for traditional risk factors, CKD-specific risk factors and level of proteinuria, and with atherosclerotic and non-atherosclerotic MACE segregated. ResultsDuring 2.9 years median follow-up, 349 people (39%) experienced a MACE. Forty-eight proteins were associated with MACE in the Discovery cohort; 9 of these were reproduced in the Replication cohort. Three of these proteins maintained a strong association with MACE after adjustment for traditional and CKD-specific risk factors, and proteinuria. Tenascin (TNC), fibroblast growth factor-23 (FGF-23) and V-set and Immunoglobulin Domain containing protein 2 (VSIG2) were associated with both atherosclerotic and non-atherosclerotic MACE. All replicated proteins except carbonic anhydrase 1 and carbonic anhydrase 3 were associated with non-atherosclerotic MACE. LimitationsSingle protein concentration measurements and limited follow up time. ConclusionsOur findings corroborate previously reported relationships between FGF-23, vascular cell adhesion protein-1, TNC and placental growth factor with cardiovascular outcomes in CKD. We identify 5 proteins not previously linked with MACE in CKD, that may be targets for future therapies.

Systemic Proteomic Analysis Reveals Distinct Exosomal Protein Profiles in Rheumatoid Arthritis.

Objective Rheumatoid arthritis (RA) is a complex disease with unknown pathogenesis. In recent years, fewer have paid attention to the broad spectrum of systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA. Methods Totally, 12 specimens of plasma from 6 RA patients and 6 age- and gender-matched controls from the Chinese population were obtained for nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis to identify exosomal profiles. Results A total of 278 exosomal proteins were detected. Among them, 32 proteins were significantly upregulated (FC ≥ 2.0 and P < 0.05) and 5 proteins were downregulated (FC ≤ 0.5 and P < 0.05). Bioinformatics analysis revealed that transthyretin (TTR), angiotensinogen (AGT), lipopolysaccharide-binding protein (LBP), monocyte differentiation antigen CD14 (CD14), cartilage oligomeric matrix protein (COMP), serum amyloid P (SAP/APCS), and tenascin (TNC) can interact with each other. Subsequently, these cross-linked proteins may be mainly involved in the inflammatory-related pathways to mediate the onset of RA. Noteworthy, the LBP/CD14 complex can promote the expression of IL-8 and TNF-α, eventually leading to the development of RA. Conclusions Our findings suggest distinct plasmatic exosomal protein profiles in RA patients. These proteins not only take important parts in the vicious circle in the pathogenic process of RA but also serve as novel biomarkers in RA diagnosis and prognosis.

Biocompatibility and immunolabeling of fibronectin and tenascin of resinous root canal sealers.

Aims:The aim of this study was to evaluate the biocompatibility of resinous root canal sealers: Sealer 26, AH plus, and SK Seal Root Canal Sealer in the subcutaneous tissue of rats.Subjects and Methods:Twenty-four Wistar rats received polyethylene tubes containing the sealers and empty tubes as control (n = 6). After 7, 15, 30, and 60 days, animals were killed and polyethylene tubes were removed with the surrounding tissues. The specimens were embedded in paraffin, processed for hematoxylin-eosin and immunohistochemistry assessed for fibronectin (FN) and tenascin (TN).Statistical Analysis Used:Data were tabulated and analyzed via Kruskal–Wallis and Dunn's test (P < 0.05).Results:All groups induced a moderate inflammatory reaction after 7 and 15 days (P > 0.05); after 30 days, a mild inflammatory infiltrate was observed in control groups, and moderate in sealers groups (P > 0.05); all groups showed mild inflammatory infiltrate at 60 days (P > 0.05). Overall, the fibrous capsule was considered thick only on the 7th day and became thin over time. All groups had expression for FN and TN in all analyzed periods, with high immunolabeling in sealers groups when comparing with the control group (P < 0.05).Conclusion:All sealers demonstrated biocompatibility and induced FN and TN expression.

Biologically Active TNIIIA2 Region in Tenascin-C Molecule: A Major Contributor to Elicit Aggressive Malignant Phenotypes From Tumors/Tumor Stroma.

Tenascin (TN)-C is highly expressed specifically in the lesions of inflammation-related diseases, including tumors. The expression level of TN-C in tumors and the tumor stroma is positively correlated with poor prognosis. However, no drugs targeting TN-C are currently clinically available, partly because the role of TN-C in tumor progression remains controversial. TN-C harbors an alternative splicing site in its fibronectin type III repeat domain, and its splicing variants including the type III-A2 domain are frequently detected in malignant tumors. We previously identified a biologically active region termed TNIIIA2 in the fibronectin type III-A2 domain of TN-C molecule and showed that this region is involved in promoting firm and persistent cell adhesion to fibronectin. In the past decade, through the exposure of various cell lines to peptides containing the TNIIIA2 region, we have published reports demonstrating the ability of the TNIIIA2 region to modulate distinct cellular activities, including survival/growth, migration, and invasion. Recently, we reported that the signals derived from TNIIIA2-mediated β1 integrin activation might play a crucial role for inducing malignant behavior of glioblastoma (GBM). GBM cells exposed to the TNIIIA2 region showed not only exacerbation of PDGF-dependent proliferation, but also acceleration of disseminative migration. On the other hand, we also found that the pro-inflammatory phenotypic changes were promoted when macrophages are stimulated with TNIIIA2 region in relatively low concentration and resulting MMP-9 upregulation is needed to release of the TNIIIA2 region from TN-C molecule. With the contribution of TNIIIA2-stimulated macrophages, the positive feedback spiral loop, which consists of the expression of TN-C, PDGF, and β1 integrin, and TNIIIA2 release, seemed to be activated in GBM with aggressive malignancy. Actually, the growth of transplanted GBM grafts in mice was significantly suppressed via the attenuation of β1 integrin activation. In this review, we thus introduce that the TNIIIA2 region has a significant impact on malignant progression of tumors by regulating cell adhesion. Importantly, it has been demonstrated that the TNIIIA2 region exerts unique biological functions through the extremely strong activation of β1-integrins and their long-lasting duration. These findings prompt us to develop new therapeutic agents targeting the TNIIIA2 region.

Periostin, tenascin, osteopontin isoforms in long- and non-long survival patients with pancreatic cancer: a pilot study.

Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the pancreas. Extracellular matrix (ECM), plays a critical role during the process of human carcinogenesis and the possible diversity in matricellular proteins composition of ECM may have a significant impact on the clinical course of PDAC. Aim of this paper was to evaluate the expression of three matricellular proteins, including Periostin (POSTN), Tenascin (TNS) and Osteopontin (OPN), in PDAC from long-survival (LS) and non-long survival (NLS) patients. A total of 30 PDAC were analyzed, 15 from patients that survived more than 60 months after surgery (LS) and 15 that died from the disease within 24 (NLS). RNA was extracted and OPN, TNS and POSTN mRNA levels were evaluated by qRT-PCR.LS and NLS samples showed the same type of POSTN and TN isoforms. On the contrary, OPN seems to be preferentially expressed in NLS PDAC. Moreover, OPNb and OPNc isoforms were expressed exclusively in NLS samples. In conclusion, Our data led to hypothesize a possible relationship between the expression of different isoforms of each of these proteins and the clinical outcome of patients with PDAC.

Expression of Fibronectin and Tenascin after Direct Capping of the Pulp with Mineral Trioxide Aggregate and Biodentine®

BACKGROUND: Caries is a destructive process leading to progressive demineralization of the inorganic part of the tooth, accompanied by enzyme disintegration of the organic component of the tooth tissue. Considering the fact that caries activity can be stopped if the demineralization process is stopped, it is clear that the objectives of caries treatment are focused toward elimination of etiological factors and stimulation of regeneration of the dental tissues. That is why in the last years treatment of the caries disease is targeted to remineralization of the initial carious lesions, as well as on the biological behavior of the pulp-dentine complex after application of certain medications.&#x0D; AIM: The aim of this study is to evaluate impact of the two materials for direct capping, mineral trioxide aggregate (MTA) and Biodentine®, on the expression of glycoproteins fibronectin (FN), and tenascin (TN), responsible for dentinogenesis.&#x0D; METHODS: In the tests were used materials MTA and Biodentine, as agents for direct capping of pulp exposure. From 60 extracted teeth included in this in vitro study, tissue cuts were made. Each of them was then analyzed on a light microscope to determine the amount of two extracellular matrix glycoproteins, FN-C, and TN-C.&#x0D; RESULTS: Our study show that there is an expressed immunoreactivity for FN and for TN in the fibronectin bridge under MTA and Biodentine® after 8, and even after 30 days of their application.&#x0D; CONCLUSION: Based on this study, we can conclude that both materials – MTA and Biodentine – may induce reparative dentinogenesis, in which FN and TN have certainly a major role in the formation of the fibronectin matrix.

Loss of Tenascin-X expression during tumor progression: A new pan-cancer marker

Cancer is a systemic disease involving multiple components produced from both tumor cells themselves and surrounding stromal cells. The pro- or anti-tumoral role of the stroma is still under debate. Indeed, it has long been considered the main physical barrier to the diffusion of chemotherapy by its dense and fibrous nature and its poor vascularization. However, in murine models, the depletion of fibroblasts, the main ExtraCellular Matrix (ECM)-producing cells, led to more aggressive tumors even though they were more susceptible to anti-angiogenic and immuno-modulators. Tenascin-C (TNC) is a multifunctional matricellular glycoprotein (i.e. an ECM protein also able to induce signaling pathway) and is considered as a marker of tumor expansion and metastasis. However, the status of other tenascin (TN) family members and particularly Tenascin-X (TNX) has been far less studied during this pathological process and is still controversial. Herein, through (1) in silico analyses of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and (2) immunohistochemistry staining of Tissue MicroArrays (TMA), we performed a large and extensive study of TNX expression at both mRNA and protein levels (1) in the 6 cancers with the highest incidence and mortality in the world (i.e. lung, breast, colorectal, prostate, stomach and liver) and (2) in the cancers for which sparse data regarding TNX expression already exist in the literature. We thus demonstrated that, in most cancers, TNX expression is significantly downregulated during cancer progression and we also highlighted, when data were available, that high TNXB mRNA expression in cancer is correlated with a good survival prognosis.

Analysis of different proteins in primary open angle glaucoma based on aqueous proteome

Objective To analyze the changes of protein expression in aqueous humor of patients with primary open angle glaucoma (POAG), and to explore the biological markers and potential therapeutic targets associated with disease occurrence. Methods A retrospective case-control study was adopted.Ten patients with age-related cataract and 10 patients with POAG combined with cataract.were collected at the Tianjin Medical University Eye Hospital from October 2016 to December 2017.In the process of surgery, 100 μl of aqueous humor were collected with 1 ml syringe and No.1 needle through the surgical access.Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry.The differential significance test was performed by Maxquant significances A. The differential proteins of the two groups were screened and determined with the conditions of P 2.The biological big data was annotated by the function of GO and KEGG.The study was approved by the Ethics Committee of the Tianjin Medical University Eye Hospital (No.2013KY[L]-10). Patients and their guardians all signed the informed consent. Results Ninty-seven differential proteins were detected in this proteomic analysis, including 48 up-regulated proteins and 49 down-regulated proteins.GO analysis significantly differs in protein function involved in many aspects, some different proteins including lipopolysaccharide-binding protein (LBP), cluster of Differentiation 163(CD163), C-reactive protein (CRP), annexin A1 (ANXA1) were involved in inflammation; redox-related proteins were glutathione S-transferase P (GSTP1), thioredoxin (TXN), some different proteins related with cell adhesion movement were cartilage oligomeric matrix protein (COMP), desmocollin-2 (DSC2) and laminin subunit beta-2 (LAMB2); procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1), solid protein (tenascin, TNC) are associated with fibrosis; some different proteins related to nerve growth were reelin (RELN), semaphorin-3F(SEMA3F), semaphorin-4B(SEMA4B). Metabolism-related proteins included pyruvate kinase (PKM), carb oxypeptidase N subunit 2 (CPN2) and so on.KEGG analysis indicated that the expression of NrF2/ERK signaling pathway and TGF-β/NF-κB signaling pathway were different between the two groups. Conclusions The expression of GSTP1 and TXN in the aqueous humor of POAG is significantly decreased, which may regulate cell adhesion and activity and expression of extracellular matrix by regulating NrF2/ERK1/2 and TGF-β/NF-κB signaling pathways.GSTP1 and TXN may serve as a potential biomarker and therapeutic target of POAG. Key words: Primary open angle glaucoma; Aqueous humor; Label free quantitative proteome; Glutathione S-transferase P; Thioredoxin; Transforming growth factor-β; nuclear factor-kappa B; Nuclear factor erythroid 2-related factor 2; extracellular regulated protein kinases

A Collagen and Silk Scaffold for Improved Healing of the Tendon and Bone Interface in a Rabbit Model.

BackgroundThe study aimed to develop a novel orthopedic surgical scaffold made of collagen and silk to repair the tendon and bone interface, and to investigate its influence on tendon and bone healing in a rabbit model.Material/MethodsFour types of surgical scaffold were prepared, including a random collagen scaffold (RCS), an aligned collagen scaffold (ACS), a random collagen scaffold combined with knitted silk (RCSS), and an aligned collagen scaffold combined with knitted silk (ACSS). Rabbit bone marrow stem cells (BMSCs) were cultured and seeded onto the RCS and ACS scaffold. The animal model included four-month-old female New Zealand White rabbits (N=20) that underwent drilling into the rotator cuff of the left supraspinatus muscle tendon, randomized into the ACSS and RCSS groups.ResultsRabbit BMSCs adhered to and proliferated on the RCS and ACS in vitro. Transcription levels of the COL I, COL III, and tenascin (TCN) genes were significantly increased in the ACS group compared with the RCS group. Transcription levels of COL I, runt-related transcription factor-2 (RUNX-2) and bone morphogenetic protein-2 (BMP-2) were significantly increased in the RCS group compared with the ACS group. RCSS and ACSS implanted in the rabbit models for eight weeks resulted in more regenerative tissue in the RCSS group compared with the ACSS group, with new cartilage at the tendon and bone interface at 12 weeks.ConclusionsA collagen and silk scaffold improved healing of the tendon and bone interface in a rabbit model.

Caveolin-1-containing extracellular vesicles transport adhesion proteins and promote malignancy in breast cancer cell lines.

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths in women worldwide, whereby mortality is largely attributable to the development of distant metastasis. Caveolin-1 (CAV1) is a multifunctional membrane protein that is typically upregulated in the final stages of cancer and promotes migration and invasion of tumor cells. Elevated levels of CAV1 have been detected in extracellular vesicles (EVs) from advanced cancer patients. EVs are lipid enclosed vesicular structures that contain bioactive proteins, DNA and RNAs, which can be transferred to other cells and promote metastasis. Therefore, we hypothesized that CAV1 containing EVs released from breast cancer cells may enhance migration and invasion of recipient cells. EVs were purified from conditioned media of MDA-MB-231 wild-type (WT), MDA-MB-231 (shCAV1; possessing the plasmid pLKO.1 encoding a 'small hairpin' directed against CAV1) and MDA-MB-231 (shC) short hairpin control cells. Nanoparticle tracking analysis revealed an average particle size of 40-350nm for all preparations. As anticipated, CAV1 was detected in MDA-MB-231 WT and shC EVs, but not in MDA-MB-231 (shCAV1) EVs. Mass spectrometry analysis revealed the presence of specific cell adhesion-related proteins, such as Cyr61, tenascin (TNC) and S100A9 only in WT and shC, but not in shCAV1 EVs. Importantly, EVs containing CAV1 promoted migration and invasion of cells lacking CAV1. We conclude that the presence of CAV1 in EVs from metastatic breast cancer cells is associated with enhanced migration and invasiveness of recipient cells in vitro, suggesting that intercellular communication promoted by EVs containing CAV1 will likely favor metastasis in vivo.

Studying Tenascin-C in systemic lupus erythematosus as a new biomarker for disease activity

Background The precise etiology and pathogenesis of systemic lupus erythematosus (SLE) remain unclear. Unpredictable flares and remissions and diverse serological and clinical manifestations are observed among patients with SLE and the challenge for the evaluation of disease activity and administration of appropriate treatment. Assessment of Tenascin-C (TNC) may reflect disease activity and/or early tissue damage in SLE. Aim The aim of this study was to examine whether TNC levels are useful as a predictive biomarker in SLE and to reflect their activity. Patients and methods In all, 50 patients with SLE (25 patients with active SLE, 25 patients with inactive SLE), and 25 age-matched and sex-matched healthy controls were enrolled in the study. Patients undergo clinical and laboratory assessment. Serum TNC was assessed by enzyme-linked immunosorbent assay. Our results The results have shown that patients with active SLE had a higher TNC level compared with inactive patients and healthy volunteers. Also the study showed a statistically significant positive correlation between TNC level and Systemic Lupus Erythematosus Disease Activity Index score. On the other hand, the TNC level correlated negatively with white blood cells, platelet counts, C3 and C4 levels, hemoglobin level, and disease status. Conclusion The increased serum tenascin level was found in patients with SLE and was correlated with certain clinical and laboratory immunoinflammatory parameters. So the estimation of serum Tenascin levels seems beneficial in the assessment of disease activity and progress in SLE patients as well as in the assessment of the efficacy of various treatment regimens used.

ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway.

There are different polarization states of macrophages, including the classically activated M1 phenotype and the alternatively activated M2 phenotype. These have different functions in the inflammation process. Activating transcription factor 3 (ATF3) is a key transcriptional regulator that inhibits the inflammatory response. However, the effects of ATF3 on migration and anti‑inflammatory control mechanisms of macrophages have not been thoroughly investigated. The present study investigated the effect of ATF3 on macrophage migration and M1/M2 polarization. Results revealed that overexpression of ATF3 promoted macrophage migration and the expression of the M2 phenotype markers [cluster of differentiation (CD) 163, mannose receptor C type 1, arginase 1 and peroxisome proliferator‑activated receptor γ] and inhibited expression of the M1 phenotype markers (monocyte chemoattractant protein‑1, inducible nitric oxide synthase, CD16 and tumor necrosis factor‑α), whereas knockdown of ATF3 resulted in a contrary effect. In addition, the wingless‑type MMTV integration site family member (Wnt)/β‑catenin signaling pathway was activated and the expression level of tenascin (TNC) was significantly upregulated by overexpression of ATF3. Additionally, inhibition of Wnt/β‑catenin signaling significantly attenuated the upregulatory effect of ATF3 on TNC. Finally, the effect of ATF3 on macrophage migration and markers of the M1 or M2 state was investigated using TNC‑specific siRNA. In conclusion, the results of the present study suggested that ATF3 promotes macrophage migration and reverses M1‑polarized macrophages to the M2 phenotype by upregulation of TNC via the Wnt/β‑catenin signaling pathway.

Tenogenic induction of equine mesenchymal stem cells by means of growth factors and low-level laser technology.

Tendons regenerate poorly due to a dense extracellular matrix and low cellularity. Cellular therapies aim to improve tendon repair using mesenchymal stem cells and tenocytes; however, a current limitation is the low proliferative potential of tenocytes in cases of severe trauma. The purpose of this study was to develop a method useful in veterinary medicine to improve the differentiation of Peripheral Blood equine mesenchymal stem cells (PB-MSCs) into tenocytes. PB-MSCs were used to study the effects of the addition of some growth factors (GFs) as TGFβ3 (transforming growth factor), EGF2 (Epidermal growth factor), bFGF2 (Fibroblast growth factor) and IGF-1 (insulin-like growth factor) in presence or without Low Level Laser Technology (LLLT) on the mRNA expression levels of genes important in the tenogenic induction as Early Growth Response Protein-1 (EGR1), Tenascin (TNC) and Decorin (DCN). The singular addition of GFs did not show any influence on the mRNA expression of tenogenic genes whereas the specific combinations that arrested cell proliferation in favour of differentiation were the following: bFGF2+TGFβ3 and bFGF2+TGFβ3+LLLT. Indeed, the supplement of bFGF2 and TGFβ3 significantly upregulated the expression of Early Growth Response Protein-1 and Decorin, while the use of LLLT induced a significant increase of Tenascin C levels. In conclusion, the present study might furnish significant suggestions for developing an efficient approach for tenocyte induction since the external administration of bFGF2 and TGFβ3, along with LLLT, influences the differentiation of PB-MSCs towards the tenogenic fate.

Does Tenascin have Clinical Implications in Pathological Grade of Glioma Patients?: A Systematic Meta-Analysis.

Tenascin (TN) is an extracellular oligomeric glycoprotein that participates in the adhesion of cells to extracellular matrixc (ECM). Studies have shown that the expression levels of TN are upregulated in a variety of cancers, including colon cancer, lung cancer, brain tumor, and breast cancer. However, the implications and utilities of TN in clinical grading and prognosis of glioma patients were seldom reported and the effects of its pathway are still unclear and controversial. Thus, it is essential to carry out a meta-analysis to draw a convincing conclusion.A literature search was carried out up to April 2015. Data was collected using a purpose-designed form including glioma's WHO grade, etc. Differences were expressed as odds ratios (ORs) or standard mean differences (SMDs) with 95% confidence intervals (CIs). Galbr figure, Cochran's Q test, and I2 test were all performed to judge the heterogeneity between included studies. To examine the stability of the pooled results, a sensitivity analysis was performed. Potential publication bias was assessed by visual inspection of funnel plot. As this meta-analysis, as a systematic review, does not involve animal experiments or direct human trials, there is no need to conduct special ethic review and the ethical approval is not necessary.In this meta-analysis, 8 eligible studies involving 456 patients were incorporated. Six studies with dichotomous data revealed TN overexpression in glioma tissues and/or surrounding neoplastic vessels was closely associated with high WHO grade (III + IV) (odds ratio 3.398, 95% confidence interval 1.933, 5.974; P = 0.000); three continuous data studies showed there were close statistical associations between TN and WHO grade (SMD −2.114, 95% CI −2.580, −1.649; P = 0.000) too. Sensitivity analysis indicated a statistically robust result. No publication bias was revealed.Our meta-analysis suggests that TN expression is potentially associated with higher WHO grade of gliomas. More evidences on the basis of the evidence-based medicine are needed to prove it.

Immunoexpression of tenascin as a predictor of the malignancy potential of oral leukoplakia associated with a tobacco habit

Oral leukoplakia is a morphological alteration of tissue that is an early indicator for malignancy. Tenascin (TN) is a large hexameric extracellular matrix (ECM) protein with anti-adhesive properties that fosters cell migration during development, wound healing and tissue remodeling; it is present in small amounts in adult tissues. Overexpression of TN in a pathological condition may be either a cause or a consequence of the disease. We evaluated the efficacy of TN for early prediction of tobacco-associated oral cancers. We studied retrospectively 95 cases of oral leukoplakia, including mild, moderate and severe cases, using immunohistochemistry for TN. We evaluated the intensity, area and pattern of TN expression. Greater intensity and area of TN expression was observed in mild and severe dysplasia than in moderate dysplasia. Most cases showed a reticular pattern of expression, especially in mild and moderate dysplasia; a fibrillar pattern was more evident in severe dysplasia. We also observed homogeneous expression pattern in some cases. TN is a marker for dysplastic changes in epithelium and its expression may be helpful for predicting the malignancy potential of tobacco-associated oral leukoplakia.

Tenascin-X: beyond the architectural function

Tenascin-X is the largest member of the tenascin (TN) family of evolutionary conserved extracellular matrix glycoproteins, which also comprises TN-C, TN-R and TN-W. Among this family, TN-X is the only member described so far to exert a crucial architectural function as evidenced by a connective tissue disorder (a recessive form of Ehlers-Danlos syndrome) resulting from a loss-of-function of this glycoprotein in humans and mice. However, TN-X is more than an architectural protein, as it displays features of a matricellular protein by modulating cell adhesion. However, the cellular functions associated with the anti-adhesive properties of TN-X have not yet been revealed. Recent findings indicate that TN-X is also an extracellular regulator of signaling pathways. Indeed, TN-X has been shown to regulate the bioavailability of the Transforming Growth Factor (TGF)-β and to modulate epithelial cell plasticity. The next challenges will be to unravel whether the signaling functions of TN-X are functionally linked to its matricellular properties.