Negative regulation of lymphangiogenesis by Tenascin-C delays the resolution of inflammation.

Lymphatic vessels are required for the clearance of excess fluid and immune cells from inflamed tissue, making the regulation of lymphangiogenesis an important area of research. Although the positive regulatory mechanisms of lymphangiogenesis are well known, the negative regulatory mechanisms observed during inflammation remain unclear. Here, we identify tenascin-C (TNC) as a spatiotemporal negative regulator of lymphangiogenesis during inflammation.

Clinical Significance of Plasma Tenascin-C Levels in Recipients With Prolonged Jaundice After Living Donor Liver Transplantation.

Background: Focusing on tenascin-C (TNC), whose expression is enhanced during the tissue remodeling process, the present study aimed to clarify whether plasma TNC levels after living donor liver transplantation (LDLT) could be a predictor of irreversible liver damage in the recipients with prolonged jaundice (PJ).

Methods: Among 123 adult recipients who underwent LDLT between March 2002 and December 2016, the subjects were 79 recipients in whom we could measure plasma TNC levels preoperatively (pre-) and on postoperative days 1 to 14 (POD1 to POD14). Prolonged jaundice was defined as serum total bilirubin level >10 mg/dL on POD14, and 79 recipients were divided into 2 groups: 56 in the non-PJ (NJ) group and 23 in the PJ group.

Inhibition of AMPA (α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate) Receptor Reduces Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

Activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) is thought to cause acute brain injury, but the role remains poorly understood in subarachnoid hemorrhage (SAH). This study was conducted to evaluate if AMPAR activation induces acute blood-brain barrier (BBB) disruption after SAH. C57BL/6 male adult mice (n = 117) underwent sham or filament perforation SAH modeling, followed by a random intraperitoneal injection of vehicle or two dosages (1 mg/kg or 3 mg/kg) of a selective noncompetitive AMPAR antagonist perampanel (PER) at 30 min post-modeling.

Generation of Transgenic Mice that Conditionally Overexpress Tenascin-C.

Tenascin-C (TNC) is an extracellular matrix glycoprotein that is expressed during embryogenesis. It is not expressed in normal adults, but is up-regulated under pathological conditions. Although TNC knockout mice do not show a distinct phenotype, analyses of disease models using TNC knockout mice combined with experiments revealed the diverse functions of TNC.

Tenascin-C in Osteoarthritis and Rheumatoid Arthritis.

Tenascin-C (TNC) is a large multimodular glycoprotein of the extracellular matrix that consists of four distinct domains. Emerging evidence suggests that TNC may be involved in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the current understanding of the role of TNC in cartilage and in synovial biology, across both OA and RA.

Tenascin-C in cardiac disease: a sophisticated controller of inflammation, repair, and fibrosis.

Tenascin-C (TNC) is a large extracellular matrix glycoprotein classified as a matricellular protein that is generally upregulated at high levels during physiological and pathological tissue remodeling and is involved in important biological signaling pathways. In the heart, TNC is transiently expressed at several important steps during embryonic development and is sparsely detected in normal adult heart but is re-expressed in a spatiotemporally restricted manner under pathological conditions associated with inflammation, such as myocardial infarction, hypertensive cardiac fibrosis, myocarditis, dilated cardiomyopathy, and Kawasaki disease. Despite its characteristic and spatiotemporally restricted expression, TNC knockout mice develop a grossly normal phenotype.

Tenascin-C Induces Phenotypic Changes in Fibroblasts to Myofibroblasts with High Contractility through the Integrin αvβ1/Transforming Growth Factor β/SMAD Signaling Axis in Human Breast Cancer.

Tenascin-C (TNC) is strongly expressed by fibroblasts and cancer cells in breast cancer. To assess the effects of TNC on stromal formation, we examined phenotypic changes in human mammary fibroblasts treated with TNC. The addition of TNC significantly up-regulated α-smooth muscle actin (α-SMA) and calponin.

TNIIIA2, The Peptide of Tenascin-C, as a Candidate for Preventing Articular Cartilage Degeneration.

Objective: TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model.

Design: Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis.

Toll-Like Receptor 4 and Tenascin-C Signaling in Cerebral Vasospasm and Brain Injuries After Subarachnoid Hemorrhage.

Toll-like receptor 4 (TLR4) is expressed in various cell types in the central nervous system and exerts maximal inflammatory responses among the TLR family members. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of a cerebral aneurysm, and therefore its activation is reasonable as an initial step of cascades to brain injuries after aneurysmal subarachnoid hemorrhage (SAH). TLR4 activation induces tenascin-C (TNC), a representative of matricellular proteins that are a class of inducible, nonstructural, secreted, and multifunctional extracellular matrix glycoproteins.

Tenascin-C promotes the repair of cartilage defects in mice.

Background: The effects of tenascin-C (TNC) on cartilage repair were examined in cartilage defect model mice. An in vitro study was also performed to determine the mechanism of cartilage repair with TNC.

Methods: Full-thickness osteochondral defects were filled with TNC (group A: 100 μg/ml, group B: 10 μg/ml, group C: empty).

Successful Inflammation Imaging of Non-Human Primate Hearts Using an Antibody Specific for Tenascin-C.

Inflammation after myocardial infarction (MI) may be a major factor influencing ventricular remodeling, leading to congestive heart failure and arrhythmia. Therefore, inflammation in the heart needs to be monitored. Tenascin-C (TNC) is an extracellular matrix molecule not normally expressed, but it is strongly upregulated when associated with active inflammation.

Tenascin-C accelerates adverse ventricular remodelling after myocardial infarction by modulating macrophage polarization.

Aims: Tenascin-C (TN-C) is an extracellular matrix protein undetected in the normal adult heart, but expressed in several heart diseases associated with inflammation. We previously reported that serum TN-C levels of myocardial infarction (MI) patients were elevated during the acute stage, and that patients with high peak TN-C levels were at high risk of left ventricular (LV) remodelling and poor outcome, suggesting that TN-C could play a significant role in the progression of ventricular remodelling. However, the detailed molecular mechanisms associated with this process remain unknown.

Tenascin-C in brain injuries and edema after subarachnoid hemorrhage: Findings from basic and clinical studies.

Subarachnoid hemorrhage (SAH) by a rupture of cerebral aneurysms remains the most devastating cerebrovascular disease. Early brain injury (EBI) is increasingly recognized to be the primary determinant for poor outcomes, and also considered to cause delayed cerebral ischemia (DCI) after SAH. Both clinical and experimental literatures emphasize the impact of global cerebral edema in EBI as negative prognostic and direct pathological factors.

Deficiency of Tenascin-C Alleviates Neuronal Apoptosis and Neuroinflammation After Experimental Subarachnoid Hemorrhage in Mice.

Tenascin-C (TNC), a matricellular protein, is upregulated in brain parenchyma after experimental subarachnoid hemorrhage (SAH). Recent studies emphasize that early brain injury (EBI) should be overcome to improve post-SAH outcomes. The aim of this study was to investigate effects of TNC knockout (TNKO) on neuronal apoptosis and neuroinflammation, both of which are important constituents of EBI after SAH.

Clinical Significance of Histological Effect and Intratumor Stromal Expression of Tenascin-C in Resected Specimens After Chemoradiotherapy for Initially Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma.

Objectives: Tenascin-C (TN-C) is an extracellular matrix protein that is up-regulated in pancreatic ductal adenocarcinoma (PDAC) stroma and associated with tumor invasion. We examined intratumor stromal expression of TN-C in resected specimens and the histologic effect of chemoradiotherapy (CRT) as prognostic indicators in initially locally advanced unresectable (UR-LA) PDAC.

Methods: Among 110 UR-LA PDAC patients enrolled in the CRT protocol from February 2005 to December 2015, 46 who underwent curative-intent resection were classified as high (tumor destruction >50%) and low (≤50%) responders according to the Evans grading system.

Peritoneal Dialysis Fluid-Induced Fragmentation of Golgi Apparatus as a Biocompatibility Marker.

In vitro biocompatibility assessments that consider physiologically appropriate conditions of cell exposure to peritoneal dialysis fluids (PDFs) are still awaited. In this study, we found that fragmentation of Golgi apparatus occurred in a pH-dependent manner within 30-min exposure to five distinct commercially available PDFs, which showed no marked difference in their effects on cell viability in the conventional MTT assay. Fluorescence microscopy analysis of labeling antibody against cis-Golgi protein GM130 indicated that the stacked cisternal structure was maintained in the perinuclear area of both M199 culture medium and a neutral-pH PDF groups.

Tenascin-C Prevents Articular Cartilage Degeneration in Murine Osteoarthritis Models.

Objective The objective of this study was to determine whether intra-articular injections of tenascin-C (TNC) could prevent cartilage damage in murine models of osteoarthritis (OA). Design Fluorescently labeled TNC was injected into knee joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4 weeks postinjection. To investigate the effects of TNC on cartilage degeneration after surgery to knee joints, articular spaces were filled with 100 μg/mL (group I), 10 μg/mL (group II) of TNC solution, or control (group III).

Tadalafil Improves L-NG-Nitroarginine Methyl Ester-Induced Preeclampsia With Fetal Growth Restriction-Like Symptoms in Pregnant Mice.

Background: We investigated the efficacy and mechanisms of tadalafil, a selective phosphodiesterase 5 inhibitor, in treating preeclampsia (PE) with fetal growth restriction (FGR) using L-NG-nitroarginine methyl ester (L-NAME)-induced PE with FGR in pregnant mice as our experimental model.

Methods: C57BL/6 mice were divided into 2 groups 11 days postcoitum (d.p.

Role of tenascin-C in articular cartilage.

Tenascin-C (TN-C) is a glycoprotein component of the extracellular matrix (ECM). TN-C consists of four distinct domains, including the tenascin assembly domain, epidermal growth factor-like repeats, fibronectin type III-like repeats, and the fibrinogen-like globe (FBG) domain. This review summarizes the role of TN-C in articular cartilage.

Effects of Tenascin-C Knockout on Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Mice.

A matricellular protein tenascin-C (TNC) has been suggested to play a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), but the direct evidence remains lacking. In this study, we examined effects of TNC knockout (TNKO) on cerebral vasospasm after experimental SAH in mice. C57BL/6 wild-type (WT) or TNKO mice were subjected to SAH by endovascular puncture.

Role of Periostin in Early Brain Injury After Subarachnoid Hemorrhage in Mice.

Background And Purpose: A matricellular protein tenascin-C is implicated in early brain injury after experimental subarachnoid hemorrhage (SAH). This study first evaluated the role of another matricellular protein periostin and the relationships with tenascin-C in post-SAH early brain injury.

Methods: Wild-type (n=226) and tenascin-C knockout (n=9) C57BL/6 male adult mice underwent sham or filament perforation SAH modeling.

Serum Tenascin-C as a Novel Predictor for Risk of Coronary Artery Lesion and Resistance to Intravenous Immunoglobulin in Kawasaki Disease - A Multicenter Retrospective Study.

Background: Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is heavily upregulated at sites of inflammation. We conducted a retrospective study to assess the utility of TN-C as a novel biomarker to predict the risk of developing coronary artery lesions (CAL) and resistance to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD).

Methods and results: We collected blood samples of 111 KD patients (IVIG-responder: 89, IVIG-resistant: 22; CAL: 8) and 23 healthy controls, and measured the serum levels of TN-C.

Epidermal growth factor-like repeats of tenascin-C-induced constriction of cerebral arteries via activation of epidermal growth factor receptors in rats.

Tenascin-C (TNC), one of matricellular proteins, has been suggested to be involved in cerebral vasospasm after aneurysmal subarachnoid hemorrhage. However, the mechanisms of how TNC constricts cerebral arteries remain unclear. The aim of this study was to examine if epidermal growth factor (EGF)-like repeats of TNC is involved in TNC-induced constriction of cerebral arteries in rats via EGF receptor (EGFR) activation.

Aneurysm Organization Effects of Gellan Sulfate Core Platinum Coil with Tenascin-C in a Simulated Clinical Setting and the Possible Mechanism.

Background: This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting.

Methods: Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm-occlusion status was evaluated angiographically and histologically at 2 weeks post coiling.