A Systems Biology Approach to Investigating Beneficial Effects of Endurance Exercise in Myositis Patients

Jessica Boehler^1,2, Marshall Hogarth³, Matthew Barberio³, Svetlana Ghimbovschi², Kristy Brown^1,2, Li Alemo Munters⁴, Ingela Loell⁴, Yi-Wen Chen^2,5, Helene Alexanderson⁶, Ingrid E. Lundberg⁷ and Kanneboyina Nagaraju^5,8, ¹Department of Integrative Systems Biology, The George Washington University, Washingtion, DC, ²Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, ³Research Center for Genetic Medicine, Children's National Medical Center, Washingtion, DC, ⁴Karolinska University Hospital, Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Sweden, Stockholm, Sweden, ⁵Department of Integrative Systems Biology, The George Washington University, Washington, DC, ⁶Department of NVS, Division of Physical Therapy, Karolinska Institutet, Huddinge, Sweden, ⁷Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, ⁸Research Center for Genetic Medicine, Children’s National Medical Center, Washington, DC

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: exercise and myositis, MicroRNA

Session Information

Date: Sunday, November 13, 2016

Title: Genetics, Genomics and Proteomics - Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Polymyositis (PM) and dermatomyositis (DM) are skeletal muscle disorders characterized by proximal muscle weakness and inflammation. Recent studies have suggested that endurance exercise improves disease activity in PM and DM by suppressing inflammation and promoting muscle growth through activation of an aerobic muscle phenotype. The molecular mechanisms underlying disease improvement are not fully understood. We hypothesized that endurance exercise induces alterations in skeletal muscle microRNAs that control genes and proteins relevant to disease pathogenesis.

Methods: Patients, diagnosed as PM or DM according to the Bohan and Peter classification, were randomized into a 12-week endurance exercise group that consisted of cycling for 1 hour/3 times a week or a non-exercised control group. Muscle biopsies from the vastus lateralis were collected before and after the 12-week training program. MicroRNA expression profiling was determined using the Affymetrix platform, mRNA using the Illumina platform and proteomics using SuperSILAC mass spectrometry. Post intervention values were normalized to pre-intervention values and a t-test for unequal variance comparing exercised vs. control patients was used to determine significant changes (p<0.05). Ingenuity Pathway Analysis (IPA) MicroRNA Target Filter was used to identify gene targets. Gene expression profiling and proteomics were used to verify microRNA targets that were altered by exercise in the patients’ skeletal muscle. IPA Core Analysis was used to determine the function of significantly changed transcripts and proteins.

Results: Endurance exercise differentially altered 188 microRNAs. Approximately one fourth of these microRNAs are predicted to target over 12,000 genes. We have found that endurance exercise alters microRNAs that affect various processes involved in the pathogenesis of myositis. MicroRNA-target transcripts altered after endurance exercise control genes that affect vasculature, inflammatory cells and skeletal muscle cells. We also found that anti-inflammatory, anti-fibrotic, and muscle regenerative and metabolic processes are affected favorably. MicroRNA-targeted proteomic analysis of these samples further confirmed that these pathways are altered at the protein level.

Conclusion: To our knowledge, this is the first systems biology study investigating microRNA, and its regulation on mRNA and protein, before and after exercise in myositis patients. Identified microRNAs can serve as biomarkers to assess disease progression, as well as monitor responses to therapy.

Disclosure: J. Boehler, None; M. Hogarth, None; M. Barberio, None; S. Ghimbovschi, None; K. Brown, None; L. Alemo Munters, None; I. Loell, None; Y. W. Chen, None; H. Alexanderson, None; I. E. Lundberg, Bristol-Myers Squibb, 2,Bristol-Myers Squibb, 5,Idera, 5,AstraZeneca, 2,ATyr, 9; K. Nagaraju, None.

To cite this abstract in AMA style:

Boehler J, Hogarth M, Barberio M, Ghimbovschi S, Brown K, Alemo Munters L, Loell I, Chen YW, Alexanderson H, Lundberg IE, Nagaraju K. A Systems Biology Approach to Investigating Beneficial Effects of Endurance Exercise in Myositis Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/a-systems-biology-approach-to-investigating-beneficial-effects-of-endurance-exercise-in-myositis-patients/. Accessed .

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