Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Neurology, Huashan hospital, Shanghai, China.
J Clin Lab Anal. 2022 Oct;36(10):e24631. doi: 10.1002/jcla.24631. Epub 2022 Aug 28.
The objective was to investigate the expression of the cGAS-STING pathway-associated protein in idiopathic inflammatory myopathy (IIM) and to investigate whether it is related to myofiber atrophy/necrosis in patients with dermatomyositis and immune-mediated necrotizing myopathy.
Muscle specimens obtained by open biopsy from 26 IIM patients (14 with dermatomyositis (DM), 8 with immune-mediated necrotizing myopathy (IMNM), and 4 with other types of IIM), 4 dystrophinopathy, and 9 control patients were assessed for expression of cGAS-STING pathway members via Western blot, quantitative real-time PCR analysis (qRT-PCR), and immunochemistry. Meanwhile, analysis its location distribution througn immunochemistry.
Compared to the control group, the expression of cGAS, STING, and related molecules was obviously increased in muscle samples of IIM patients. Upregulated cGAS and STING were mainly located in the vascular structure, inflammatory infiltrates, and atrophic and necrotic fibers. While comparing to the Dys patients, the mRNA level of cGAS, STING, and TNF-a was upregulated, meanwhile, the protein of the TBK1, P-TBK1, and P-IRF3 associated with interferon upregulation was overexpressed through Western blot in IMNM and DM. Considering that cGAS and STING are located in necrotic and Mx1-positive atrophic fibers, it is really possible that the cGAS-STING pathway may lead to fibers atrophy/necrosis by producing IFNs.
The cGAS-STING pathway was activated in the muscle samples of IIM patients and its activation may be the reason of myofiber atrophy and necrosis in DM and IMNM patients.
本研究旨在探讨环鸟苷酸-腺苷酸合成酶（cGAS）-STING 通路相关蛋白在特发性炎性肌病（IIM）中的表达情况，并探讨其与皮肌炎和免疫介导性坏死性肌病患者肌纤维萎缩/坏死的关系。
通过开放性肌肉活检获得 26 例 IIM 患者（14 例皮肌炎（DM），8 例免疫介导性坏死性肌病（IMNM），4 例其他类型的 IIM）、4 例肌营养不良症和 9 例对照组患者的肌肉标本，通过 Western blot、实时定量 PCR 分析（qRT-PCR）和免疫化学法评估 cGAS-STING 通路成员的表达。同时，通过免疫化学法分析其位置分布。
与对照组相比，IIM 患者的肌肉样本中 cGAS、STING 及其相关分子的表达明显增加。上调的 cGAS 和 STING 主要位于血管结构、炎症浸润和萎缩坏死纤维中。与 Dys 患者相比，IMNM 和 DM 患者的 cGAS、STING 和 TNF-a 的 mRNA 水平上调，同时 Western blot 结果显示与干扰素上调相关的 TBK1、P-TBK1 和 P-IRF3 蛋白表达过度。考虑到 cGAS 和 STING 位于坏死和 Mx1 阳性萎缩纤维中，cGAS-STING 通路通过产生 IFNs 导致纤维萎缩/坏死的可能性确实存在。
cGAS-STING 通路在 IIM 患者的肌肉样本中被激活，其激活可能是 DM 和 IMNM 患者肌纤维萎缩和坏死的原因。
