Xin is a marker of skeletal muscle damage severity in myopathies.
Xin is a striated muscle-specific protein that is localized to the myotendinous junction in skeletal muscle. However, in injured mouse muscle, Xin expression is up-regulated and observed throughout skeletal muscle fibers and within satellite cells. In this study, Xin was analyzed by immunofluorescent staining in skeletal muscle samples from 47 subjects with various forms of myopathy, including muscular dystrophies, inflammatory myopathies, mitochondrial/metabolic myopathy, and endocrine myopathy. Results indicate that Xin immunoreactivity is positively and significantly correlated (rs = 0.6175, P = <0.0001) with the severity of muscle damage, regardless of myopathy type. Other muscle damage measures also showed a correlation with severity [Xin actin-binding repeat-containing 2 (rs = -0.7108, P = 0.0006) and collagen (rs = 0.4683, P = 0.0783)]. However, because only Xin lacked immunoreactivity within the healthy muscle belly, any detectable immunoreactivity for Xin was indicative of muscle damage. We also investigated the expression of Xin within the skeletal muscle of healthy individuals subjected to damaging eccentric exercise. Consistent with our previously mentioned results, Xin immunoreactivity was increased 24 hours after exercise in damaged muscle fibers and within the activated muscle satellite cells. Taken together, these data demonstrate Xin as a useful biomarker of muscle damage in healthy individuals and in patients with myopathy. The strong correlation between the degree of muscle damage and Xin immunoreactivity suggests that Xin may be a suitable outcome measure to evaluate disease progression and treatment effects in clinical trials.
Department of Medicine and Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Mats I
MI
Nilsson
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Aliyah A
AA
Nissar
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Dhuha
D
Al-Sajee
Department of Medicine and Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Mark A
MA
Tarnopolsky
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
Gianni
G
Parise
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Boleslav
B
Lach
Institute for Cell Biology, University of Bonn, Bonn, Germany.
Dieter O
DO
Fürst
Institute for Cell Biology, University of Bonn, Bonn, Germany.
Peter F M
PFM
van der Ven
Department of Neurology, Neuromuscular Centre Ruhrgebiet, University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
Rudolf A
RA
Kley
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: hawke@mcmaster.ca.
Thomas J
TJ
Hawke
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index
D015415:Biomarkers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C512114:XIRP1 protein, human