2. Academic Validation
  3. microRNA-125b-1-3p mediates autophagy via the RRAGD/mTOR/ULK1 signaling pathway and mitigates atherosclerosis progression

microRNA-125b-1-3p mediates autophagy via the RRAGD/mTOR/ULK1 signaling pathway and mitigates atherosclerosis progression

  • Cell Signal. 2024 Mar 11:118:111136. doi: 10.1016/j.cellsig.2024.111136.
Xin Chen 1,  Yanhong Cao 1,  Yining Guo 1,  Jing Liu 2,  Xiaohan Ye 3,  Huan Li 2,  Lu Zhang 2,  Wenwei Feng 3,  Shaoxiang Xian 2,  Zhongqi Yang 2,  Lingjun Wang 4,  Ting Wang 5
Affiliations

Affiliations

  • 1 Dongguan Hospital, Guangzhou University of Chinese Medicine, Dongguan, China; Guangzhou University of Chinese Medicine, Guangzhou, China; State Key Laboratory of Traditional Chinese Medicine Syndromes, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 2 Guangzhou University of Chinese Medicine, Guangzhou, China; State Key Laboratory of Traditional Chinese Medicine Syndromes, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 Dongguan Hospital, Guangzhou University of Chinese Medicine, Dongguan, China; Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 4 Guangzhou University of Chinese Medicine, Guangzhou, China; State Key Laboratory of Traditional Chinese Medicine Syndromes, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: smu868@163.com.
  • 5 Dongguan Hospital, Guangzhou University of Chinese Medicine, Dongguan, China; Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: 270177997@qq.com.
PMID: 38471617 DOI: 10.1016/j.cellsig.2024.111136
Abstract

Atherosclerosis is characterised by lipid accumulation and formation of foam cells in arterial walls. Dysregulated Autophagy is a crucial factor in atherosclerosis development. The significance of MicroRNA (miR)-125b-1-3p in Cardiovascular Disease is well-established; however, its precise role in regulating Autophagy and impact on atherosclerosis in vascular smooth muscle cells (VSMCs) remain unclear. Here, we observed reduced autophagic activity and decreased miR-125b expression during atherosclerosis progression. miR-125b-1-3p overexpression significantly reduced atherosclerotic plaque development in mice; it also led to decreased lipid uptake and deposition in VSMCs, enhanced Autophagy, and suppression of smooth muscle cell phenotypic changes in-vitro. An interaction between miR-125b-1-3p and the RRAGD/mTOR/ULK1 pathway was revealed, elucidating its role in promoting Autophagy. Therefore, miR-125b-1-3p plays a pivotal role in enhancing autophagic processes, inhibiting foam cell formation in VSMCs and mitigating atherosclerosis progression, partly through RRAGD/mTOR/ULK1 signaling axis modulation. Thus, miR-125b-1-3p is a promising target for preventive and therapeutic strategies for atherosclerosis.

Keywords

Atherosclerosis; Autophagic activity; RRAGD/mTOR/ULK1 pathway; miR-125b-1-3p.

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