Browsing by Subject "TWEAK"

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    Inhibition of the TWEAK/Fn14 pathway attenuates autoimmune arthritis in a SKG mouse model
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Park, Jin Sil; Kim, Sung Min; Jung, Kyung Ah; Lee, Jennifer; Kwok, Seung Ki; Cho, Mi La; Park, Sung Hwan
    Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a proinflammatory cytokine that is involved in pathogenesis of abnormal or disregulated inflammation. To verify how TWEAK/fibroblast growth factor-inducible gene 14 (Fn14) signals affect development of Th17 cells in arthritis, we utilized the SKG mouse, which spontaneously develops Th17- mediated autoimmune arthritis. Fn14-Fc was administered to zymosan A-induced arthritogenic SKG mice, and the effects in vivo were examined. Destruction of cartilage and bone damage was assessed by Hematoxylin and Eosin, and safranin O staining of the affected tissues. Phenotypic analysis of cells expressing inflammatory cytokines and angiogenesis-related factors, and the expression of transcription factor STAT3 in the affected joints were determined by immunohistochemistry. Blockade of Fn14 with Fn14-Fc reduced the clinical and histologic scores of inflammatory arthritis in the mouse model of spontaneously developed chronic autoimmune arthritis. Fn14-Fc suppressed production of inflammatory cytokines and angiogenesis-promoting factors, such as vascular endothelial growth factor and matrix metalloproteinase 3. Moreover, blocking of the TWEAK signal inhibited expression of STAT3 as well as interleukin-17 and -21 produced by Th17 cells. These results implicate TWEAK as a potential molecular target for treatment or prevention of inflammatory arthritis and autoimmune diseases such as rheumatoid arthritis.
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    TWEAK and NT-proBNP levels predict exercise capacity in hypertrophic cardiomyopathy
    (Wiley, 2015-02) Jover, Eva; Andreu Cayuelas, José M.; Romero Aniorte, Ana I.; Casas, Teresa; Cánovas López, Sergio; Montero Argudo, José A.; Valdés, Mariano; Morena, Gonzalo de la; Marín, Francisco; Martínez Cáceres, Carlos Manuel; Orenes-Piñero, Esteban; Hernández Romero, Diana; Cirugía, Pediatría y Obstetricia y Ginecología
    Background Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, myocyte disarray and increased interstitial fibrosis. The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a cell surface cytokine with biological activities including stimulation of cell growth, induction of inflammatory cytokines and stimulation of apoptosis. There are controversial data about the potential role of TWEAK in different cardiovascular pathologies. NT-proBNP is an established biomarker of myocardial wall stress, associated with poor functional class in HCM. We hypothesized that effort capacity in patients with HCM could be related to serum levels of these biomarkers. Materials and methods We included 40 haemodynamic stable HCM patients and 53 healthy controls with similar sex and age. We studied exercise capacity by maximal oxygen consumption in a limited treadmill exercise test. TWEAK and NT-proBNP were assayed by ELISA method and automated Elecsys® platform, respectively. We obtained 46 samples of myocardial tissues by septal myectomy in patients with HCM and evaluated myocardial fibrosis, immunoreaction with TWEAK antibody and apoptosis with TUNEL assay. Results We found raised TWEAK and NT-proBNP serum levels in patients when compared with control levels (both P < 0·001). In a multivariate analysis, TWEAK and NT-proBNP levels, as well as sex, remained independently associated with the effort capacity (all P < 0·05). We found an association between immunoreaction degree and the degree of myocardial fibrosis (P = 0·021), as well as apoptosis (P = 0·002) in the tissue samples from patients undergoing septal myectomy. Conclusions TWEAK and NT-proBNP levels are biomarkers of disease severity independently associated with the effort capacity in patients with HCM.
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    TWEAK/Fn14 signaling: a promising target in intervertebral disc degeneration
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Liu, Yu-Ping; Yuan, Chong-Ming; Zhang, Shuai-Gong; Hao, Qing-Hai; Wang, Ming-Ming; Zhang, Zhong; Meng, Qian; Li, Ming; Hao, Yue-Dong