特雷姆2
自噬
PI3K/AKT/mTOR通路
巨噬细胞
下调和上调
小胶质细胞
癌症研究
吞噬作用
生物
细胞生物学
信号转导
泡沫电池
炎症
医学
细胞凋亡
化学
免疫学
生物化学
体外
基因
作者
Yuling Xu,Xiaoyu Liu,Saibo Cheng,Peikun He,Mukeng Hong,Yuyao Chen,Fenghua Zhou,Yuhua Jia
标识
DOI:10.1142/s0192415x20500913
摘要
Macrophage autophagy defect is closely related to the progression of atherosclerosis (AS) and is regulated by the triggering receptor expressed on myeloid cell 2 (TREM2). TREM2 is a key factor in the development of Alzheimer’s disease (AD), the deficiency of which leads to anomalous autophagy in microglia. However, the role of TREM2 in the autophagy of plaque macrophages is still unclear. Geniposide (GP) can inhibit AS progression and enhance macrophage autophagy, although the underlying mechanisms remain unknown. We found that high-fat diet (HFD) feeding significantly increased TREM2 levels and inhibited autophagy in the macrophages of ApoE[Formula: see text] mice. TREM2 overexpression in RAW264.7 macrophages decreased autophagy via activation of mTOR signaling. GP inhibited the progression of AS in ApoE[Formula: see text] mice, reinforced macrophage autophagy, and downregulated TREM2 by inhibiting mTOR signaling. Taken together, augmenting the autophagy levels in plaque macrophages by inhibiting the TREM2/mTOR axis can potentially impede atherosclerotic progression. The promising therapeutic effects of GP seen in this study should be validated in future trials, and the underlying mechanisms have to be elucidated in greater detail.
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