Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Int J Mol Sci. 2023 Jan 27;24(3):2469. doi: 10.3390/ijms24032469.
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.
皮肌炎（DM）和免疫介导的坏死性肌病（IMNM）是两种罕见疾病，属于特发性炎症性肌病（IIM）组。DM 中的肌肉受累表现为纤维旁萎缩和肌纤维坏死不良，而 IMNM 的特征是肌纤维坏死伴少量炎症浸润。肌肉活检和实验室检查有助于诊断，但目前很少有疾病活动和进展的生物标志物。在这方面，我们对 41 名 40-70 岁的 DM 和 IMNM 患者进行了队列研究。与对照组相比，在这些患者的肌肉活检中，FNDC5（鸢尾素的前体）的表达较低，鸢尾素是一种在肌肉骨骼代谢中起关键作用的肌因子。预期这些患者的肌肉横截面积会减少，但令人惊讶的是，血清鸢尾素水平高于对照组，ADAM10（一种最近被证明是 FNDC5 切割剂的金属蛋白酶）的 mRNA 水平也是如此。我们假设，DM 和 IMNM 患者骨骼肌中 ADAM10 的高表达可能是导致鸢尾素水平与 FNDC5 表达之间差异的原因。未来的研究将需要了解这些炎症性肌病中 FNDC5 切割加剧和肌肉鸢尾素抵抗的机制。
