PMID- 33406428
OWN - NLM
STAT- MEDLINE
DCOM- 20211206
LR  - 20211214
IS  - 2211-1247 (Electronic)
VI  - 34
IP  - 1
DP  - 2021 Jan 5
TI  - Expression of miRNA-29 in Pancreatic beta Cells Promotes Inflammation and Diabetes 
      via TRAF3.
PG  - 108576
LID - S2211-1247(20)31565-5 [pii]
LID - 10.1016/j.celrep.2020.108576 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is recognized as a chronic, low-grade 
      inflammatory disease characterized by insulin resistance and pancreatic beta cell 
      dysfunction; however, the underlying molecular mechanism remains unclear. Here, 
      we report a key beta cell-macrophage crosstalk pathway mediated by the 
      miRNA-29-TNF-receptor-associated factor 3 (TRAF3) axis. beta 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 beta 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 beta cells to 
      modulate the systemic inflammatory tone and glucose homeostasis via miR-29 in 
      response to nutrient overload.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Sun, Yi
AU  - Sun Y
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and 
      Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
FAU - Zhou, Yuncai
AU  - Zhou Y
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and 
      Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
FAU - Shi, Ying
AU  - Shi Y
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and 
      Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and 
      Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
FAU - Liu, Kerong
AU  - Liu K
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and 
      Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
FAU - Liang, Rui
AU  - Liang R
AD  - Organ Transplant Center, Tianjin First Central Hospital, Nankai University, 
      Tianjin 300192, China.
FAU - Sun, Peng
AU  - Sun P
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and 
      Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
FAU - Chang, Xiaoai
AU  - Chang X
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and 
      Molecular Biology, Nanjing medical University, Nanjing, Jiangsu 211166, China.
FAU - Tang, Wei
AU  - Tang W
AD  - Department of Endocrinology, Geriatric Hospital of Nanjing Medical University, 
      Nanjing, Jiangsu 210024, China.
FAU - Zhang, Yujing
AU  - Zhang Y
AD  - 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.
FAU - Li, Jing
AU  - Li J
AD  - 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.
FAU - Wang, Shusen
AU  - Wang S
AD  - Organ Transplant Center, Tianjin First Central Hospital, Nankai University, 
      Tianjin 300192, China.
FAU - Zhu, Yunxia
AU  - Zhu Y
AD  - 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.
FAU - Han, Xiao
AU  - Han X
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Insulin)
RN  - 0 (MIRN29 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (TNF Receptor-Associated Factor 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Diabetes Mellitus, Experimental/metabolism
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Diet, High-Fat
MH  - Exosomes/metabolism
MH  - Glucose/metabolism
MH  - Glucose Intolerance/metabolism
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Insulin-Secreting Cells/*metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - MicroRNAs/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - *Signal Transduction
MH  - TNF Receptor-Associated Factor 3/*metabolism
OTO - NOTNLM
OT  - TRAF3
OT  - chronic inflammation
OT  - exosome
OT  - glucose metabolism
OT  - insulin resistance
OT  - metabolic stress
OT  - miR-29
OT  - monocytes and macrophages
OT  - type 2 diabetes mellitus
OT  - beta cell dysfunction
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2021/01/07 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/01/06 20:04
PHST- 2020/06/22 00:00 [received]
PHST- 2020/10/23 00:00 [revised]
PHST- 2020/12/09 00:00 [accepted]
PHST- 2021/01/06 20:04 [entrez]
PHST- 2021/01/07 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
AID - S2211-1247(20)31565-5 [pii]
AID - 10.1016/j.celrep.2020.108576 [doi]
PST - ppublish
SO  - Cell Rep. 2021 Jan 5;34(1):108576. doi: 10.1016/j.celrep.2020.108576.