Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus.
Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus.
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肌遗传学寡脱氧核苷酸（MyODN）恢复了糖尿病麦芽脂质恶化的骨骼肌成肌细胞的分化。
DOI：
10.3389/fphys.2021.679152
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发表时间：
2021
影响因子：
4
通讯作者：
Takaya T
中科院分区：
文献类型：
--
作者：
Nakamura S;Yonekura S;Shimosato T;Takaya T
糖尿病（DM）患者的骨骼肌萎缩是肌肉质量和力量下降的并发症，是可能导致死亡的严重危险因素。 DM 患者中肌肉前体细胞（称为成肌细胞）的分化恶化被认为是肌肉萎缩的原因之一。我们最近开发了肌发生寡脱氧核苷酸 (myoDN)，它是 18 个碱基的单链 DNA，可通过靶向核仁素促进成肌细胞分化。在此，我们报告了 myoDN（iSN04）对从 1 型和 2 型 DM 患者分离的成肌细胞的适用性。 DM 成肌细胞的肌生成随着肌源转录的延迟转变和白细胞介素的诱导而加剧。在用过量葡萄糖或棕榈酸培养的健康成肌细胞中再现了类似的表型，模拟高血糖或高脂血症。 iSN04治疗通过下调肌生长抑制素和白细胞介素8（IL-8）来恢复多个DM成肌细胞恶化的分化。 iSN04 还可以改善由葡萄糖或棕榈酸诱导的受损的生肌分化。这些结果表明，myoDNs 可以直接促进 DM 患者的成肌细胞分化，使其成为治疗 DM 患者肌肉萎缩的核酸药物的新候选者。
Skeletal muscle wasting in patients with diabetes mellitus (DM) is a complication of decreased muscle mass and strength, and is a serious risk factor that may result in mortality. Deteriorated differentiation of muscle precursor cells, called myoblasts, in DM patients is considered to be one of the causes of muscle wasting. We recently developed myogenetic oligodeoxynucleotides (myoDNs), which are 18-base single-strand DNAs that promote myoblast differentiation by targeting nucleolin. Herein, we report the applicability of a myoDN, iSN04, to myoblasts isolated from patients with type 1 and type 2 DM. Myogenesis of DM myoblasts was exacerbated concordantly with a delayed shift of myogenic transcription and induction of interleukins. Analogous phenotypes were reproduced in healthy myoblasts cultured with excessive glucose or palmitic acid, mimicking hyperglycemia or hyperlipidemia. iSN04 treatment recovered the deteriorated differentiation of plural DM myoblasts by downregulating myostatin and interleukin-8 (IL-8). iSN04 also ameliorated the impaired myogenic differentiation induced by glucose or palmitic acid. These results demonstrate that myoDNs can directly facilitate myoblast differentiation in DM patients, making them novel candidates for nucleic acid drugs to treat muscle wasting in patients with DM.
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