Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance
Dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necro...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2469 |
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| author | Roberta Zerlotin Marco Fornaro Mariella Errede Patrizia Pignataro Clelia Suriano Maddalena Ruggieri Silvia Colucci Florenzo Iannone Maria Grano Graziana Colaianni |
| author_facet | Roberta Zerlotin Marco Fornaro Mariella Errede Patrizia Pignataro Clelia Suriano Maddalena Ruggieri Silvia Colucci Florenzo Iannone Maria Grano Graziana Colaianni |
| author_sort | Roberta Zerlotin |
| collection | DOAJ |
| description | Dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necrosis with scarce inflammatory infiltrates. Muscle biopsies and laboratory tests are helpful in diagnosis, but currently, few biomarkers of disease activity and progression are available. In this context, we conducted a cohort study of forty-one DM and IMNM patients, aged 40–70 years. In comparison with control subjects, in the muscle biopsies of these patients, there was a lower expression of FNDC5, the precursor of irisin, a myokine playing a key role in musculoskeletal metabolism. Expectedly, the muscle cross-sectional areas of these patients were reduced, while, surprisingly, serum irisin levels were higher than in CTRL, as were mRNA levels of ADAM10, a metalloproteinase recently shown to be the cleavage agent for FNDC5. We hypothesize that elevated expression of ADAM10 in the skeletal muscle of DM and IMNM patients might be responsible for the discrepancy between irisin levels and FNDC5 expression. Future studies will be needed to understand the mechanisms underlying exacerbated FNDC5 cleavage and muscle irisin resistance in these inflammatory myopathies. |
| first_indexed | 2024-03-11T09:41:01Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:41:01Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8ec4271d9eb9459e8e71647816276bc62023-11-16T16:57:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243246910.3390/ijms24032469Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin UnbalanceRoberta Zerlotin0Marco Fornaro1Mariella Errede2Patrizia Pignataro3Clelia Suriano4Maddalena Ruggieri5Silvia Colucci6Florenzo Iannone7Maria Grano8Graziana Colaianni9Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, ItalyDermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necrosis with scarce inflammatory infiltrates. Muscle biopsies and laboratory tests are helpful in diagnosis, but currently, few biomarkers of disease activity and progression are available. In this context, we conducted a cohort study of forty-one DM and IMNM patients, aged 40–70 years. In comparison with control subjects, in the muscle biopsies of these patients, there was a lower expression of FNDC5, the precursor of irisin, a myokine playing a key role in musculoskeletal metabolism. Expectedly, the muscle cross-sectional areas of these patients were reduced, while, surprisingly, serum irisin levels were higher than in CTRL, as were mRNA levels of ADAM10, a metalloproteinase recently shown to be the cleavage agent for FNDC5. We hypothesize that elevated expression of ADAM10 in the skeletal muscle of DM and IMNM patients might be responsible for the discrepancy between irisin levels and FNDC5 expression. Future studies will be needed to understand the mechanisms underlying exacerbated FNDC5 cleavage and muscle irisin resistance in these inflammatory myopathies.https://www.mdpi.com/1422-0067/24/3/2469irisinFNDC5ADAM10myopathydermatomyositisimmune-mediated necrotizing myopathy |
| spellingShingle | Roberta Zerlotin Marco Fornaro Mariella Errede Patrizia Pignataro Clelia Suriano Maddalena Ruggieri Silvia Colucci Florenzo Iannone Maria Grano Graziana Colaianni Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance International Journal of Molecular Sciences irisin FNDC5 ADAM10 myopathy dermatomyositis immune-mediated necrotizing myopathy |
| title | Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance |
| title_full | Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance |
| title_fullStr | Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance |
| title_full_unstemmed | Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance |
| title_short | Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance |
| title_sort | elevated expression of adam10 in skeletal muscle of patients with idiopathic inflammatory myopathies could be responsible for fndc5 irisin unbalance |
| topic | irisin FNDC5 ADAM10 myopathy dermatomyositis immune-mediated necrotizing myopathy |
| url | https://www.mdpi.com/1422-0067/24/3/2469 |
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