Article ; Online: 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
2023 Volume 24, Issue 3
Abstract: 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, ...
Abstract | 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. |
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MeSH term(s) | Humans ; Fibronectins/metabolism ; Cohort Studies ; Muscle, Skeletal/metabolism ; Myositis/metabolism ; Transcription Factors/metabolism ; Autoimmune Diseases/metabolism ; Necrosis/metabolism ; ADAM10 Protein/genetics ; ADAM10 Protein/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Amyloid Precursor Protein Secretases/metabolism |
Chemical Substances | Fibronectins ; Transcription Factors ; ADAM10 protein, human (EC 3.4.24.81) ; ADAM10 Protein (EC 3.4.24.81) ; Membrane Proteins ; Amyloid Precursor Protein Secretases (EC 3.4.-) ; FNDC5 protein, human |
Language | English |
Publishing date | 2023-01-27 |
Publishing country | Switzerland |
Document type | Journal Article |
ZDB-ID | 2019364-6 |
ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
ISSN (online) | 1422-0067 |
ISSN | 1422-0067 ; 1661-6596 |
DOI | 10.3390/ijms24032469 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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