2. Academic Validation
  3. Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3

Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3

  • Cell Rep. 2021 Jan 5;34(1):108576. doi: 10.1016/j.celrep.2020.108576.
Yi Sun 1,  Yuncai Zhou 1,  Ying Shi 1,  Yan Zhang 1,  Kerong Liu 1,  Rui Liang 2,  Peng Sun 1,  Xiaoai Chang 1,  Wei Tang 3,  Yujing Zhang 4,  Jing Li 4,  Shusen Wang 2,  Yunxia Zhu 5,  Xiao Han 6
Affiliations

Affiliations

  • 1 Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
  • 2 Organ Transplant Center, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.
  • 3 Department of Endocrinology, Geriatric Hospital of Nanjing Medical University, Nanjing, Jiangsu 210024, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210046, China.
  • 5 Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China. Electronic address: zhuyx@njmu.edu.cn.
  • 6 Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China. Electronic address: hanxiao@njmu.edu.cn.
PMID: 33406428 DOI: 10.1016/j.celrep.2020.108576
Abstract

Type 2 diabetes mellitus (T2DM) is recognized as a chronic, low-grade inflammatory disease characterized by Insulin resistance and pancreatic β cell dysfunction; however, the underlying molecular mechanism remains unclear. Here, we report a key β cell-macrophage crosstalk pathway mediated by the miRNA-29-TNF-receptor-associated factor 3 (TRAF3) axis. β cell-specific transgenic miR-29a/b/c mice are predisposed to develop glucose intolerance and Insulin resistance when fed a high-fat diet (HFD). The metabolic effect of β cell miR-29 is largely mediated through macrophages because either depletion of macrophages or reconstitution with miR-29-signaling defective bone marrow improves metabolic parameters in the transgenic mice. Mechanistically, our data show that miR-29 promotes the recruitment and activation of circulating monocytes and macrophages and, hence, inflammation, via miR-29 exosomes in a TRAF3-dependent manner. Our results demonstrate the ability of β cells to modulate the systemic inflammatory tone and glucose homeostasis via miR-29 in response to nutrient overload.

Keywords

TRAF3; chronic inflammation; exosome; glucose metabolism; insulin resistance; metabolic stress; miR-29; monocytes and macrophages; type 2 diabetes mellitus; β cell dysfunction.

Figures
Products
Inhibitors & Agonists
Other Products