Abstract
IntroductionThe aim of this study was to investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in patients with polymyositis (PM) and dermatomyositis (DM), and their relation to clinical manifestations.MethodsSerum levels of TWEAK were detected in 98 PM/DM patients and 37 healthy controls by using the ELISA method. Total RNA isolated from fresh-frozen muscle tissue samples of 36 PM/DM patients and 10 healthy controls were used for analyzing the mRNA levels of TWEAK and Fn14 by quantitative reverse transcription polymerase chain reaction (RT-PCR). Immunofluorescence staining of TWEAK and Fn14 was conducted on muscle biopsy specimens from 23 PM/DM patients and seven healthy controls.ResultsSerum levels of TWEAK were significantly decreased in the PM/DM patients compared to those in the healthy controls (P < 0.001), and serum TWEAK levels negatively correlated with serum CD163 levels in PM/DM patients (r = -0.49, P < 0.001). The expression of Fn14 mRNA was significantly increased in the muscle tissue of PM/DM patients than in the muscle tissue of healthy controls (P < 0.01), whereas the expression of TWEAK mRNA in PM/DM patients was not statistically different from that of the healthy controls (P > 0.05). Fn14 mRNA levels in muscle tissue positively correlated with muscle disease activity (r = 0.512, P < 0.01). Patients with oropharyngeal dysphagia had significantly higher Fn14 mRNA levels than patients without oropharyngeal dysphagia (P < 0.05). The results of immunofluorescence staining showed that 19 out of 23 PM/DM patients were TWEAK-positive, and 20 out of 23 PM/DM patients were Fn14-positive. No detectable expressions of TWEAK or Fn14 were observed in the healthy controls.ConclusionsTWEAK-Fn14 axis may be involved in the pathogenesis of PM/DM. Further understanding of TWEAK-Fn14 function in PM/DM may help to define therapeutic targets for PM/DM.
Highlights
The aim of this study was to investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in patients with polymyositis (PM) and dermatomyositis (DM), and their relation to clinical manifestations
Relative quantification mRNA analysis showed that Fn14 mRNA expression in the muscle tissue of PM/DM patients was higher than in healthy controls, and Fn14 mRNA levels positively correlated with myositis disease activity assessment visual analog scales (MYOACT) muscle disease activity scores
Taking into account molecular interaction between TWEAK and CD163 molecules, in the present study we evaluated serum CD163 levels in PM/DM patients, and we found a negative correlation between serum levels of TWEAK and CD163
Summary
The aim of this study was to investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in patients with polymyositis (PM) and dermatomyositis (DM), and their relation to clinical manifestations. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a recently identified pro-inflammatory cytokine belonging to the TNF superfamily [8]. TWEAK has emerged as a multifunctional cytokine that regulates multiple cellular responses, including pro-inflammatory activity; angiogenesis; and cell proliferation, differentiation, migration and apoptosis [9]. The only known signaling receptor for TWEAK is fibroblast growth factor-inducible 14 (Fn14), which was first recognized by differential display technique [10]. Fn14 is a type I transmembrane protein and is highly inducible by various growth factors, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Fn14 is predominantly expressed on the surface of epithelial cells, endothelial cells and other non-hematopoietic cells [9,11]
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