{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:16:53Z","timestamp":1791001013898,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"9","funder":[{"name":"Nutrition and Obesity Training Grant (NIH)","award":["5T32 DK62710"],"award-info":[{"award-number":["5T32 DK62710"]}]},{"name":"UAB Center for Clinical and Translational Science","award":["UL1 TR000165"],"award-info":[{"award-number":["UL1 TR000165"]}]},{"name":"VA Meritt Award"},{"name":"UAB Center for Exercise Medicine"},{"name":"UAB Department of Physical Medicine and Rehabilitation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:p> Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNF\u03b1R, TNF\u03b1, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-\u03baB, and p-p65\/p-50\/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (\u224822 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNF\u03b1R and TWEAK R gene expression and NF-\u03baB signaling (higher TWEAK R and phospho-NF-\u03baB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK\/TWEAK R\/NF-\u03baB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle. <\/jats:p>","DOI":"10.1152\/ajpendo.00240.2015","type":"journal-article","created":{"date-parts":[[2016,3,2]],"date-time":"2016-03-02T04:33:23Z","timestamp":1456893203000},"page":"E754-E761","source":"Crossref","is-referenced-by-count":36,"title":["Heightened TWEAK-NF-\u03baB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury"],"prefix":"10.1152","volume":"310","author":[{"given":"Ceren","family":"Yarar-Fisher","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation,"},{"name":"UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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