Journal
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
Volume 59, Issue 2, Pages 167-179Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1369/jhc.2010.956672
Keywords
congenital muscular dystrophy; laminin alpha2; LYVE-1; inflammation; tenascin C; muscle
Categories
Funding
- National Institutes of Health [R01 AR051368]
- John W. Alden Trust
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
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Congenital muscular dystrophy type 1A, a severe neuromuscular disease characterized by early-onset muscle weakness and degeneration, is caused by insufficient levels of laminin alpha 2 (LAMA2) in the basal lamina surrounding muscle fibers and other cells. A better understanding of the molecular mechanisms leading to muscle loss is needed to develop therapeutic interventions for this disease. Here, the authors show that inflammation is an early feature of pathogenesis in Lama2-deficient mouse muscle, indicated by elevated expression of tenascin C in the endomysium around muscle fibers, infiltration of macrophages, and induction of the inflammatory cytokines tumor necrosis factor alpha (TNF alpha) and IL-1 beta. In addition, the expression of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), a specific marker for lymphatic vessel endothelial cells, is dramatically reduced early in Lama2-deficient muscle pathogenesis. LYVE-1 expression, which is inhibited by TNF alpha, is also decreased in muscles undergoing degeneration due to dystrophin deficiency and cardiotoxin damage. LYVE-1 expression thus provides a useful biomarker to monitor the onset of muscle pathogenesis, likely serving as an indicator of inflammatory signals present in muscles. Together, the data show that inflammatory pathways are activated in the earliest stages of Lama2-deficient disease progression and could play a role in early muscle degeneration. (J Histochem Cytochem 59:167-179, 2011)
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