PMID- 35528840
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220510
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 9
DP  - 2022
TI  - Circulating Exosomal miR-181b-5p Promoted Cell Senescence and Inhibited 
      Angiogenesis to Impair Diabetic Foot Ulcer via the Nuclear Factor Erythroid 
      2-Related Factor 2/Heme Oxygenase-1 Pathway.
PG  - 844047
LID - 10.3389/fcvm.2022.844047 [doi]
LID - 844047
AB  - Endothelial cell dysfunction is the main contributing factor of diabetic foot 
      ulcer (DFU). Circulating exosomes have been found to play an important role in 
      many processes, such as cell senescence and angiogenesis. However, the underlying 
      roles and mechanism of circulating exosomes in the onset and progression of DFU 
      remain unclear. In this study, we isolated exosomes from the plasma of patients 
      with DFU (DFU-Exos) and non-diabetic foot wounds (NDF-Exos). DFU-Exos promoted 
      cell senescence and inhibited tube formation in Human Umbilical Vein Endothelial 
      Cells (HUVECs), unlike NDF-Exos. Several datasets suggest that miR-181b-5p 
      expression might be enriched in exosomes from DFU; this was verified using 
      quantitative real-time PCR (qRT-PCR). We also found that miR-181b-5p, which was 
      taken up by HUVECs, promoted cell senescence and inhibited tube formation. Dual 
      luciferase reporter assay, qRT-PCR, Western blotting, and immunofluorescence 
      staining confirmed that miR-181b-5p could negatively regulate nuclear factor 
      erythroid 2-related factor 2 (NRF2) expression by binding to its 3' UTR, thus 
      further suppressing heme oxygenase-1 (HO-1) expression. In addition, NRF2 and 
      HO-1 inhibitors could also rescue the effects of senescence and tube formation 
      exerted by miR-181b-5p inhibitor. In vivo experiments showed that exosomes 
      isolated from HUVECs which inhibited miR-181b-5p expression promoted angiogenesis 
      to further restore the capacity of wound healing. In conclusion, this study 
      indicated that circulating exosomal miR-181b-5p promoted cell senescence and 
      inhibited angiogenesis to impair wound healing in DFU by regulating the NRF2/HO-1 
      pathway.
CI  - Copyright (c) 2022 Wang, Shi, Zhou, Wang, Zhang and Li.
FAU - Wang, Shaohua
AU  - Wang S
AD  - Hebei Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, 
      The Second Hospital of Hebei Medical University, Shijiazhuang, China.
FAU - Shi, Min
AU  - Shi M
AD  - Hebei Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, 
      The Second Hospital of Hebei Medical University, Shijiazhuang, China.
FAU - Zhou, Jing
AU  - Zhou J
AD  - Department of Endocrinology, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, China.
FAU - Wang, Wenjing
AU  - Wang W
AD  - Hebei Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, 
      The Second Hospital of Hebei Medical University, Shijiazhuang, China.
FAU - Zhang, Yuanyuan
AU  - Zhang Y
AD  - Hebei Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, 
      The Second Hospital of Hebei Medical University, Shijiazhuang, China.
FAU - Li, Yongjun
AU  - Li Y
AD  - Hebei Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, 
      The Second Hospital of Hebei Medical University, Shijiazhuang, China.
LA  - eng
PT  - Journal Article
DEP - 20220420
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC9067436
OTO - NOTNLM
OT  - angiogenesis
OT  - diabetic foot ulcer
OT  - exosomes
OT  - miR-181b-5p
OT  - senescence (leaf)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/05/10 06:00
MHDA- 2022/05/10 06:01
PMCR- 2022/01/01
CRDT- 2022/05/09 04:01
PHST- 2022/01/13 00:00 [received]
PHST- 2022/03/24 00:00 [accepted]
PHST- 2022/05/09 04:01 [entrez]
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/05/10 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2022.844047 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Apr 20;9:844047. doi: 10.3389/fcvm.2022.844047. 
      eCollection 2022.