PMID- 38074896
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231211
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 34
DP  - 2023 Dec 12
TI  - Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by 
      targeting GDF6 to interrupt diabetic wound healing.
PG  - 102074
LID - 10.1016/j.omtn.2023.102074 [doi]
LID - 102074
AB  - Unprogrammed macrophage polarization, especially prolonged activation of 
      proinflammatory macrophages, is associated with delayed wound healing in diabetic 
      objectives. Macrophage-derived exosomes cargo a variety of microRNAs (miRNAs), 
      participating in different stages in wound healing. Here, exosomes were isolated 
      from naive bone marrow-derived macrophages (BMDMs) (M0-Exos), interferon-gamma plus 
      lipopolysaccharide-polarized BMDMs (M1-Exos), and interleukin-4-polarized BMDMs 
      (M2-Exos). M1-Exos impaired migration and tube formation in human umbilical vein 
      endothelial cells (HUVECs) compared to M0-Exos, whereas M2-Exos exhibited the 
      opposite effects. High-throughput sequencing was performed to decipher the miRNA 
      expression profiles in M0-Exos, M1-Exos, and M2-Exos. A total of 63 miRNAs were 
      identified to be differentially expressed in exosomes derived from polarized 
      BMDMs. Among them, miRNA-155-5p is highly expressed in M1-Exos, which interrupted 
      angiogenesis in HUVECs. Furthermore, miRNA-155-5p directly binds to the 3' UTR of 
      growth differentiation factor 6 (GDF6) mRNA to suppress its protein expression. 
      Lastly, local administration of a temperature-sensitive hydrogel Pluronic F-127 
      loading miRNA-155-5p antagomiR promoted angiogenesis and accelerated wound 
      healing in diabetic db/db mice via enhancing GDF6. In summary, this study 
      deciphered the miRNA expression profiles in exosomes from polarized macrophages. 
      M2-like macrophage-derived exosomes and miRNA-155-5p inhibitors could be 
      promising therapeutics against diabetic foot ulcers.
CI  - (c) 2023 The Author(s).
FAU - Lou, Ruohan
AU  - Lou R
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
FAU - Chen, Jiali
AU  - Chen J
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
FAU - Zhou, Fei
AU  - Zhou F
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
FAU - Zhang, Tian
AU  - Zhang T
AD  - Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common 
      Chronic Diseases, Guizhou Medical University, Guiyang 550025, China.
FAU - Chen, Xiuping
AU  - Chen X
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
AD  - Department of Pharmaceutical Sciences and Technology, Faculty of Health Sciences, 
      University of Macau, Taipa, Macau 999078, China.
FAU - Wang, Chunming
AU  - Wang C
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
AD  - Department of Pharmaceutical Sciences and Technology, Faculty of Health Sciences, 
      University of Macau, Taipa, Macau 999078, China.
FAU - Guo, Bing
AU  - Guo B
AD  - Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common 
      Chronic Diseases, Guizhou Medical University, Guiyang 550025, China.
FAU - Lin, Ligen
AU  - Lin L
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
AD  - Department of Pharmaceutical Sciences and Technology, Faculty of Health Sciences, 
      University of Macau, Taipa, Macau 999078, China.
LA  - eng
PT  - Journal Article
DEP - 20231110
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC10701080
OTO - NOTNLM
OT  - MT: Oligonucleotides: Therapies and Applications
OT  - angiogenesis
OT  - diabetic wound healing
OT  - growth differentiation factor 6
OT  - microRNA expression profiles
OT  - polarized macrophage-derived exosomes
OT  - thermosensitive hydrogel
COIS- The authors declare no competing interests.
EDAT- 2023/12/11 06:45
MHDA- 2023/12/11 06:46
PMCR- 2023/11/10
CRDT- 2023/12/11 05:49
PHST- 2023/08/30 00:00 [received]
PHST- 2023/11/08 00:00 [accepted]
PHST- 2023/12/11 06:46 [medline]
PHST- 2023/12/11 06:45 [pubmed]
PHST- 2023/12/11 05:49 [entrez]
PHST- 2023/11/10 00:00 [pmc-release]
AID - S2162-2531(23)00292-5 [pii]
AID - 102074 [pii]
AID - 10.1016/j.omtn.2023.102074 [doi]
PST - epublish
SO  - Mol Ther Nucleic Acids. 2023 Nov 10;34:102074. doi: 10.1016/j.omtn.2023.102074. 
      eCollection 2023 Dec 12.