PMID- 31867895
OWN - NLM
STAT- MEDLINE
DCOM- 20210208
LR  - 20210208
IS  - 1613-6829 (Electronic)
IS  - 1613-6810 (Linking)
VI  - 16
IP  - 3
DP  - 2020 Jan
TI  - Circulating Exosomal miR-20b-5p Inhibition Restores Wnt9b Signaling and Reverses 
      Diabetes-Associated Impaired Wound Healing.
PG  - e1904044
LID - 10.1002/smll.201904044 [doi]
AB  - At present, developing therapeutic strategies to improve wound healing in 
      individuals with diabetes remains challenging. Exosomes represent a promising 
      nanomaterial from which microRNAs (miRNAs) can be isolated. These miRNAs have the 
      potential to exert therapeutic effects, and thus, determining the potential 
      therapeutic contributions of specific miRNAs circulating in exosomes is of great 
      importance. In the present study, circulating exosomal miRNAs are identified in 
      diabetic patients and assessed for their roles in the context of diabetic wound 
      healing. A significant upregulation of miR-20b-5p is observed in exosomes 
      isolated from patients with type 2 diabetes mellitus (T2DM), and this miRNA is 
      able to suppress human umbilical vein endothelial cell angiogenesis via 
      regulation of Wnt9b/beta-catenin signaling. It is found that the application of 
      either miR-20b-5p or diabetic exosomes to wound sites is sufficient to slow wound 
      healing and angiogenesis. In diabetic mice, it is found that knocking out 
      miR-20b-5p significantly enhances wound healing and promotes wound angiogenesis. 
      Together, these findings thus provide strong evidence that miR-20b-5p is highly 
      enriched in exosomes from patients with T2DM and can be transferred to cells of 
      the vascular endothelium, where it targets Wnt9b signaling to negatively regulate 
      cell functionality and angiogenesis.
CI  - (c) 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Xiong, Yuan
AU  - Xiong Y
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Chen, Lang
AU  - Chen L
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Yan, Chenchen
AU  - Yan C
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Zhou, Wu
AU  - Zhou W
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Endo, Yori
AU  - Endo Y
AD  - Department of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, MA, 02152, USA.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Hu, Liangcong
AU  - Hu L
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Hu, Yiqiang
AU  - Hu Y
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Mi, Bobin
AU  - Mi B
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
FAU - Liu, Guohui
AU  - Liu G
AUID- ORCID: 0000-0002-2013-1396
AD  - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191223
PL  - Germany
TA  - Small
JT  - Small (Weinheim an der Bergstrasse, Germany)
JID - 101235338
RN  - 0 (MIRN20b microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (WNT9B protein, human)
RN  - 0 (Wnt Proteins)
SB  - IM
MH  - Animals
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/metabolism/*physiopathology
MH  - Exosomes/*metabolism
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Mice
MH  - MicroRNAs/*antagonists & inhibitors/blood
MH  - Wnt Proteins/*metabolism
MH  - *Wound Healing
OTO - NOTNLM
OT  - exosomes
OT  - miR-20b-5p
OT  - type 2 diabetes
OT  - wounds
EDAT- 2019/12/24 06:00
MHDA- 2021/02/09 06:00
CRDT- 2019/12/24 06:00
PHST- 2019/07/25 00:00 [received]
PHST- 2019/11/19 00:00 [revised]
PHST- 2019/12/24 06:00 [pubmed]
PHST- 2021/02/09 06:00 [medline]
PHST- 2019/12/24 06:00 [entrez]
AID - 10.1002/smll.201904044 [doi]
PST - ppublish
SO  - Small. 2020 Jan;16(3):e1904044. doi: 10.1002/smll.201904044. Epub 2019 Dec 23.