1. Academic Validation
  2. 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.
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.

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