Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: The molecular basis of myopathies such as dermatomyositis, polymyositis and inclusion-body myositis, which are characterized by chronic muscle inflammation followed by long term skeletal muscle wasting, are poorly understood.
Methods: We compared expression levels of inflammatory cytokines and microRNAs to identify those differentially expressed between muscle biopsies from myositis patients (N = 24) and healthy donors (N = 17). We then used human and mouse in vitro myoblast-to-myocyte differentiation models to determine those differentially expressed cytokines and microRNAs that affect myoblast differentiation.
Results: We observed increased expression of inflammatory cytokines including TNF-alpha (fold change = 3.8 to 8.8-fold, P-values < 0.045), and decreased expression of microRNAs miR-1 (fold changes = -2.8 to -8.7, P-values < 2.0x10-4), miR-133a (fold changes = -3.9 to -5.0, P-values < = 4.0x10-4), miR-133b (fold changes = -2.7 to -7.8, P-values <4.2x10-4), and miR-206 (DM = -2.8-fold, P = 0.012) which are known to be critical to adult skeletal muscle differentiation. TNF-alpha inhibited expression of miR-1, 133a/b, and 206 and suppressed differentiation of C2C12 myoblasts to myocytes/myotubes in an NF-kb dependent manner. This block in differentiation by TNF-alpha was relieved by overexpression of miR-1, miR-206 or miR-133
Conclusion: Taken together these results provide a new mechanistic link between a pro-inflammatory cytokine and the degenerative pathology of myositis, and suggest new therapeutic approaches for this disease.
Disclosure:
R. Georgantas III,
Medimmune, Inc,
3,
AstraZeneca,
1;
K. Streicher,
AstraZeneca,
1,
Medimmune, Inc,
3;
S. A. Greenberg,
Medimmune, Inc,
2;
L. Greenlees,
AstraZeneca,
1,
Medimmune, Inc,
3;
W. Zhu,
AstraZeneca,
1,
MedImmune,
3;
P. Brohawn,
AstraZeneca,
1,
MedImmune,
3;
B. W. Higgs,
AstraZeneca,
1,
MedImmune,
3;
M. Czapiga,
AstraZeneca,
1,
Medimmune, Inc,
1;
C. Morehouse,
AstraZeneca,
1,
MedImmune,
3;
L. Richman,
AstraZeneca,
1,
Medimmune, Inc,
3;
B. Jallal,
AstraZeneca,
1,
MedImmune,
3;
K. Ranade,
AstraZeneca,
1,
Medimmune, Inc,
3;
Y. Yao,
AstraZeneca,
1,
MedImmune,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/myositis-autoimmunity-and-muscle-weakness-are-linked-to-tnf-alpha-suppression-of-micrornas-1-133-and-206-in-myoblasts-and-myocytes/