Department of General Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
J Immunol Res. 2017;2017:3262384. doi: 10.1155/2017/3262384. Epub 2017 Jan 17.
Polymyositis (PM) is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR) signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactions lipid metabolism. In this study, we aim to figure out the role of mTOR signaling in the development of polymyositis and identify novel biomarkers for the detection and therapy of polymyositis. After screening and validation, we found that palmitoleic acid, a monounsaturated fatty acid, is highly regulated by mTOR signaling. Inhibition of mTORC1 activity decreases palmitoleic acid level. Moreover, mTORC1 regulates the level of palmitoleic acid by controlling its de novo synthesis. Importantly, increased palmitoleic acid has been proven to be a marker of polymyositis. Our work identifies palmitoleic acid in peripheral blood mononuclear cells (PBMC) as a biomarker of polymyositis and offers new targets to the clinical therapy.
多发性肌炎(PM)是一种以肌肉疼痛、无力和肌肉相关酶升高为特征的慢性疾病,伴有淋巴细胞炎症。然而,目前尚不清楚淋巴细胞中的分子改变如何导致多发性肌炎的发生。雷帕霉素靶蛋白(mTOR)信号通路是哺乳动物细胞代谢和炎症的中央调节者。基于之前的研究,我们提出 mTOR 信号通路可能控制炎症反应和脂质代谢。在这项研究中,我们旨在研究 mTOR 信号通路在多发性肌炎发展中的作用,并确定用于多发性肌炎检测和治疗的新型生物标志物。经过筛选和验证,我们发现棕榈油酸(一种单不饱和脂肪酸)受 mTOR 信号通路的高度调控。mTORC1 活性的抑制会降低棕榈油酸的水平。此外,mTORC1 通过控制棕榈油酸的从头合成来调节其水平。重要的是,已证明升高的棕榈油酸是多发性肌炎的标志物。我们的工作确定了外周血单核细胞(PBMC)中的棕榈油酸是多发性肌炎的生物标志物,并为临床治疗提供了新的靶点。