Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis.

Ayuka Murakami, Seiya Noda, Tomoyuki Kazuta, Satoko Hirano, Seigo Kimura, Hirotaka Nakanishi, Koji Matsuo, Koyo Tsujikawa, Madoka Iida, Haruki Koike, Kazuma Sakamoto, Yuichiro Hara, Satoshi Kuru, Kenji Kadomatsu, Teppei Shimamura, Tomoo Ogi, Masahisa Katsuno

Journal: Annals of clinical and translational neurology 2022;9(10):1602-1615

PMID: 36107781

Free Full Text on PubMed Central View on PubMed

Abstract

OBJECTIVE

Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients older than 50 years of age. sIBM is hardly responds to any immunosuppressing theraphies, and its pathophysiology remains elusive. This study aims to explore pathogenic pathways underlying sIBM and identify novel therapeutic targets using metabolomic and transcriptomic analyses.

METHODS

In this retrospective observational study, we analyzed biopsied muscle samples from 14 sIBM patients and six non-diseased subjects to identify metabolic profiles. Frozen muscle samples were used to measure metabolites with cation and anion modes of capillary electrophoresis time of flight mass spectrometry. We validated the metabolic pathway altered in muscles of sIBM patients through RNA sequencing and histopathological studies.

RESULTS

A total of 198 metabolites were identified. Metabolomic and transcriptomic analyses identified specific metabolite changes in sIBM muscle samples. The pathways of histamine biosynthesis and certain glycosaminoglycan biosynthesis were upregulated in sIBM patients, whereas those of carnitine metabolism and creatine metabolism were downregulated. Histopathological examination showed infiltration of mast cells and deposition of chondroitin sulfate in skeletal muscle samples, supporting the results of metabolomic and transcriptomic analyses.

INTERPRETATION

We identified alterations of several metabolic pathways in muscle samples of sIBM patients. These results suggest that mast cells, chondroitin sulfate biosynthesis, carnitine, and creatine play roles in sIBM pathophysiology.

Address: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Neurology, National Hospital Organization Suzuka Hospital, Suzuka, Japan.; Department of Neurology, Yokkaichi Municipal Hospital, Yokkaichi, Japan.; Department of Neurology, Kariya Toyota General Hospital, Kariya, Japan.; Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Institute for Glyco-Core Research (iGCORE), Nagoya University, Nagoya, Japan.; Department of Genetics, Research Institute of Environmental Medicine (RLeM), Nagoya University, Nagoya, Japan.; Department of Human Genetics and Molecular Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Neurology, National Hospital Organization Suzuka Hospital, Suzuka, Japan.; Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Department of Clinical Research Education, Nagoya University Graduate School of Medicine, Nagoya, Japan.

DOI: 10.1002/acn3.51657

Link outs

Free resources

Full Text Sources:

MeSH Terms: Carnitine, Chondroitin Sulfates, Creatine, Gene Expression Profiling, Histamine, Humans, Metabolome, Muscle, Skeletal, Myositis, Inclusion Body