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FRI0524 Elevated HMGB1 and Decreased Micrornas Expression in Polymyositis: Potential Contributions to Muscle Inflammation and Degeneration
  1. X.-M. Shu,
  2. Q.-L. Peng,
  3. X. Lu,
  4. G.-C. Wang
  1. Rheumatology, China-Japan Friendship Hospital, Beijing, China

Abstract

Background The cause of muscle weakness and inflammation has not yet been elucidated in polymyositis. Many factors other than muscle fiber damage induced by inflammatory cells and their products called damage associated with molecular patterns (DAMPs) may be the major contributors to impair muscle tissue. HMGB1 is a damage associated with molecular pattern which may be involved in inflammatory diseases. MicroRNAs (miRs) are evolutionarily conserved small RNAs that post- transcriptionally regulate gene expression and have emerged as critical regulators of skeletal muscle development. However, it is still unknown whether HMGB1 and miRs are related with inflammation and degenerative process of muscle in PM.

Objectives The aim of this study is to determine whether HMGB1 and miRs are related with inflammation and degenerative process of muscle in PM, and explore the feasibility of detecting miRs expression profiles in formalin-fixed, paraffin-embedded (FFPE) skeletal muscle tissues from PM patients.

Methods Damage associated molecular pattern HMGB1 expression was detected by immunohistochemistry. A group of miRs profiles including miR-21p, miR-23a-3p, miR-23b-3p, miR-122-5p, miR-142-3p, miR-146a-5p, miR-146-5p, miR150-5p, miR-155-5p, miR-181a-2-3p were detected by RT-PCR in skeletal muscles embedded in paraffin from 13 adult disease-onset PM patients, and 6 non-myositis muscle controls.

Results We observed increased expression of HMGB1 in polymyositis compared with non-myositis muscle tissues (P<0.05). Further, we observed decreased expression of miR-23b-3p, miR-146a-5p, miR-146-5p, as well as miR-150-5p in formalin-fixed, paraffin-embedded skeletal muscle tissues from PM patients compared with non-myositis muscle control (all P<0.005). Both elevated HMGB1 and decreased miRs were related with inflammation and degeneration of muscle in PM. Importantly, HMGB1 was significantly inversely correlated with decreased miRs expression in polymyositis.

Conclusions Our findings demonstrate the feasibility of detecting microRNA expression profiling in formalin-fixed, paraffin-embedded skeletal muscle tissues and have shown that HMGB1 was significantly inversely correlated with decreased miRs expression, which both promote muscle inflammation and degeneration in polymyosits.

References

  1. Oshikawa Y, Jinin M, Makino T, et al. Decreased miR-7 Expression in the Skin and Sera of Patients with Dermatomyositis. Acta Derm Venereol 2012; 92.

  2. Georgantas RW, Streicher K, Greenberg SA, et al. Inhibition of myogenic MicroRNAs-1, 133, and 206 by inflammatory cytokines links inflammation and muscle degeneration in adult inflammatory myopathies. Arthritis Rheum. 2013 Nov 27. doi: 10.1002/art.38292. [Epub ahead of print].

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.4025

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