The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jeon-Soo; Zheng, Timothy S.; Burkly, Linda C.; Kumar, Ashok

doi:10.1016/j.bbrc.2014.03.084

Cited by 26 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TWEAK is a member of the TNF superfamily of cytokines and an important stimulus for the activation of NF-B signaling in skeletal muscle (39,40). TWEAK R, the smallest member of the TNF superfamily, has been identified as the unique TWEAK R (28,31,35).…”

Section: E757 Heightened Tweak-tweak R-nf-b Signaling In Sci Musclementioning

confidence: 99%

“…TWEAK R is expressed at low levels in healthy tissues, and its expression significantly increases in response to injury, aging, disuse (40), and acute resistance exercise (33). Short-term TWEAK-TWEAK R activation promotes tissue repair and regeneration following an acute injury; however, during chronic injury or disease conditions, sustained TWEAK-TWEAK R activation may drive these responses toward a pathological remodeling in the muscle in which healthy tissue is replaced by fibrotic tissue (15,39,40). TWEAK-TWEAK R signaling promotes fibrogenic activities via increasing accumulation of fibroblasts (31,42) and/or increasing collagen gene expression (Col1a1 and Col1a2) (30,31) in skeletal muscle through its activation of inflammatory signaling pathways.…”

Section: E757 Heightened Tweak-tweak R-nf-b Signaling In Sci Musclementioning

confidence: 99%

“…The TWEAK-TWEAK R system is also an important regulator of fibrosis in skeletal muscle (39,40). The TWEAK-TWEAK R axis promotes fibrogenic activities through its direct action on stromal cell types, thereby causing the accumulation of myofibroblasts.…”

mentioning

confidence: 99%

“…creased levels of proinflammatory cytokines in the skeletal muscle have been emerging as potential contributors to muscle insulin resistance (13,14), impaired oxidative metabolism (35,36), increased fibrosis (39), and impaired regenerative capacity (27,32). Given that paralyzed muscle presents with extreme atrophy (11), impaired muscle metabolism (16,26), and impaired regenerative capacity (1) shortly after SCI, it is important to consider the impact of skeletal muscle inflammation on these reported muscle pathologies.…”

mentioning

confidence: 99%

“…Chronic elevation of TWEAK signaling in muscle promotes atrophy, metabolic dysfunction, and fibrogenesis (9,12,28,29,35,36). The TWEAK-TWEAK receptor (R) system mediates the activation of the NF-B signaling pathway, which leads to the increased expression of muscle RING finger 1 (MuRF1) and muscle atrophy F-box (atrogin-1), degradation of muscle proteins, including MyHC (39), and repression of peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) levels in skeletal muscle (35,36). This leads to muscle atrophy (in catabolic conditions, disuse, unloading, and aging), reduced expression of several mitochondrial genes, reduced proportion of type I fibers, and increased proportion of type II fibers.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury

Yarar‐Fisher

Bickel

Kelly

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

Section: E757 Heightened Tweak-tweak R-nf-b Signaling In Sci Musclementioning

confidence: 99%

Section: E757 Heightened Tweak-tweak R-nf-b Signaling In Sci Musclementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury

Yarar‐Fisher

Bickel

Kelly

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

TWEAK/Fn14 axis is an important player in fibrosis

Zhang

Zeng

Xia

2020

Journal Cellular Physiology

View full text Add to dashboard Cite

Fibrosis is a common pathological condition associated with abnormal repair after tissue injury. However, the etiology and molecular mechanisms of fibrosis are still not well‐understood. Tumor necrosis factor (TNF)‐like weak inducer of apoptosis (TWEAK) belongs to the TNF superfamily and acts by binding to its receptor, fibroblast growth factor‐inducible 14 (Fn14), thereby activating a variety of intracellular signal transduction pathways in various types of cells. Besides promoting the expression of growth factors, activation of TWEAK/Fn14 signaling after tissue injury can promote the expression of pro‐inflammatory cytokines, which trigger the immune response, thereby exacerbating the injury. Severe or repetitive injury leads to a dysregulated tissue repair process, in which the TWEAK/Fn14 axis promotes the activation and proliferation of myofibroblasts, induces the secretion of the extracellular matrix, and regulates profibrotic mediators to further perpetuate and sustain the fibrotic process. In this review, we summarize the available experimental evidence on the underlying molecular mechanisms by which the TWEAK/Fn14 pathway mediates the development and progression of fibrosis. In addition, we discuss the therapeutic potential of the TWEAK/Fn14 pathway in fibrosis‐associated diseases based on evidence derived from multiple models and cells from injured tissue and fibrotic tissue.

show abstract

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention

Shyh‐Chang

et al. 2019

J cachexia sarcopenia muscle

181

114

View full text Add to dashboard Cite

Background Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. Methods A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured. Results The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05). Conclusions High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could signif...

show abstract

The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

Cited by 26 publications

References 36 publications

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury

TWEAK/Fn14 axis is an important player in fibrosis

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention

Contact Info

Product

Resources

About