通过诱导 AMPK/PGC-1α 介导的线粒体生物生成,MOTS-c 是治疗链脲佐菌素诱导的糖尿病痛性神经病变的有效靶点。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Lingfei Xu, Xihui Tang, Long Yang, Min Chang, Yuqing Xu, Qingsong Chen, Chen Lu, Su Liu, Jinhong Jiang
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引用次数: 0

摘要

疼痛性糖尿病神经病变(PDN)是一种常见的糖尿病并发症,经常引起严重的痛觉减退和异动症,给治疗带来了挑战。MOTS-c是一种新型线粒体衍生肽,已被证明可以调节糖代谢、胰岛素敏感性和炎症反应。本研究旨在评估 MOTS-c 在链脲佐菌素(STZ)诱导的 PDN 模型中的作用,并研究其潜在的内在机制。我们发现,STZ 治疗小鼠血浆和脊髓背角的内源性 MOTS-c 水平明显低于对照组。因此,MOTS-c治疗能明显改善STZ诱导的体重减轻、血糖升高、机械异感和热痛。此外,MOTS-c 还能显著增强 PDN 小鼠腰脊髓中 AMPKα1/2 磷酸化和 PGC-1α 的表达。机理研究表明,MOTS-c 能明显恢复线粒体的生物生成,抑制小胶质细胞的活化,减少促炎因子的产生,从而缓解疼痛。此外,MOTS-c 还能通过激活 AMPK/PGC-1α 信号通路,降低 STZ 诱导的 PDN 小鼠痛觉过敏性。这为开发基于线粒体肽的 PDN 治疗药物提供了药理学和生物学证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MOTS-c is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of AMPK/PGC-1α -mediated mitochondrial biogenesis.
Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. MOTS-c, a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an AMPK inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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