Transcriptional profiling identifies differential expression of long non-coding RNAs in Jo-1 associated and inclusion body myositis

Abstract

Myositis is characterised by muscle inflammation and weakness. Although generally thought to be driven by a systemic autoimmune response, increasing evidence suggests that intrinsic changes in the muscle might also contribute to the pathogenesis. Long non-coding RNAs (lncRNAs) are a family of novel genes that regulate gene transcription and translation. To determine the potential role of lncRNAs, we employed next generation sequencing to examine the transcriptome in muscle biopsies obtained from two histologically distinct patient populations, inclusion body myositis (IBM) and anti-Jo-1-associated myositis (Jo-1). 1287 mRNAs and 1068 mRNAs were differentially expressed in the muscle from Jo-1 and IBM patients, respectively. Pathway analysis showed the top canonical pathway in both Jo-1 and IBM was oxidative phosphorylation and mitochondrial dysfunction. We identified 731 known and 325 novel lncRNAs in the muscles biopsies. Comparison with controls showed 55 and 46 lncRNAs were differentially expressed in IBM and Jo-1 myositis, respectively. Of these, 16 lncRNAs were differentially expressed in both IBM and Jo-1 myositis and included upregulated H19, lncMyoD and MALAT1. Given that these are known to regulate muscle proliferation and differentiation, we speculate that changes in lncRNAs might contribute to the phenotypic changes in Jo-1 and IBM myositis.

Immunohistochemical and ultrastructural analysis of sporadic inclusion body myositis: a case series

“…In most cases we saw myofiber atrophy with subsequent invasion of connective and adipose tissue. The results are in accordance with observations made by others [12,17,27,36,37]. In a few cases hypertrophic myofibers in IBM patients were also reported [12,27].…”

“…Since s-IBM is an untreatable disease establishing the final diagnosis is critical for patients in order to avoid an ineffective immunosuppressive therapy with its many side effects [9,15], and to start physiotherapy [33]. In our study the clinical features, including weakness of upper and lower extremities, difficulty in climbing stairs as well as patients' ages were typical and similar to other reports [12,27,34]. Moreover, similarly to Hermanns et al [4] and Sakai et al [17] we observed periodical increases in the levels of CK and LDH enzymes in the studied patients' serum.…”

“…Accumulated proteins have the immunoreactivity of betaamyloid, Tau protein and apolipoproteins [20,[23][24][25]. For the final diagnosis of this disease it is necessary to carry out research with a transmission electron microscope (TEM), in order to demonstrate the presence of RVs and disorganization of myofibrils [7,23,26,27].…”

Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis‐Associated Lung Adenocarcinoma Transcript 1 Long Noncoding RNA in Obese Patients With Osteoarthritis

“…In attempting to better understand the cellular regulators of synovial joint inflammation, investigators have identified long noncoding RNAs (lncRNAs) (18,19) as a central regulator of the inflammatory response (20)(21)(22)(23)(24). We recently identified lncRNAs that are associated with the inflammatory response in human OA chondrocytes, which function by regulating the secretion of proinflammatory cytokines (22,25).…”

Escalating protein supersaturation underlies inclusion formation in muscle proteinopathies

“…By contrast, of the top 5% most supersaturated proteins in this subset (N=41) (Top σ f ), seven (17%) are decreased in affected fibers (enrichment p=0.013) ( Figure 4B ). As further validation of this phenomenon, we used RNA sequencing data from healthy muscle and IBM muscle to identify the transcripts of proteins that were downregulated in IBM tissue (21). The downregulated transcripts correspond to proteins whose supersaturation scores tend to be elevated in healthy controls (median Δ: 2.6x, p=3.3•10 −3 ) ( SI Appendix, Figure S12A ).…”