PMID- 31068817
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - Resveratrol Promotes Diabetic Wound Healing via SIRT1-FOXO1-c-Myc Signaling 
      Pathway-Mediated Angiogenesis.
PG  - 421
LID - 10.3389/fphar.2019.00421 [doi]
LID - 421
AB  - Background/Aims: Diabetic non-healing skin ulcers represent a serious challenge 
      in clinical practice, in which the hyperglycemia-induced disturbance of 
      angiogenesis, and endothelial dysfunction play a crucial role. Resveratrol (RES), 
      a silent information regulator 1 (SIRT1) agonist, can improve endothelial 
      function and has strong pro-angiogenic properties, and has thus become a research 
      focus for the treatment of diabetic non-healing skin ulcers; however, the 
      underlying mechanism by which RES regulates these processes remains unclear. 
      Therefore, the present study was intended to determine if RES exerts its observed 
      protective role in diabetic wound healing by alleviating hyperglycemia-induced 
      endothelial dysfunction and the disturbance of angiogenesis. Methods: We 
      investigated the effects of RES on cell migration, cell proliferation, apoptosis, 
      tube formation, and the underlying molecular mechanisms in 33 mM high 
      glucose-stimulated human umbilical vein endothelial cells (HUVECs) by 
      semi-quantitative RT-PCR, western blot analysis, terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) staining, and 
      immunofluorescence in vitro. We further explored the role of RES on endothelial 
      dysfunction and wound healing disturbance in db/db mice by TUNEL staining, 
      immunofluorescence, and photography in vivo. Results: We observed an obvious 
      inhibition of hyperglycemia-triggered endothelial dysfunction and a disturbance 
      of angiogenesis, followed by the promotion of diabetic wound healing via RES, 
      along with restoration of the activity of the hyperglycemia-impaired SIRT1 
      signaling pathway. Pretreatment with EX-527, a SIRT1 inhibitor, abolished the 
      RES-mediated endothelial protection and pro-angiogenesis action, and then delayed 
      diabetic wound healing. Furthermore, examination of the overexpression of 
      forkhead box O1 (FOXO1), a transcription factor substrate of SIRT1, in HUVECs and 
      db/db mice revealed that RES activated SIRT1 to restore hyperglycemia-triggered 
      endothelial dysfunction and disturbance of angiogenesis, followed by the 
      promotion of diabetic wound healing in a c-Myc-dependent manner. Pretreatment 
      with 10058-F4, a c-Myc inhibitor, repressed RES-mediated endothelial protection, 
      angiogenesis, and diabetic wound healing. Conclusion: Our findings indicate that 
      the positive role of RES in diabetic wound healing via its SIRT1-dependent 
      endothelial protection and pro-angiogenic effects involves the inhibition of 
      FOXO1 and the de-repression of c-Myc expression.
FAU - Huang, Xiaozhong
AU  - Huang X
AD  - Department of Pediatric Surgery, The Second Affiliated Hospital and Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Sun, Jia
AU  - Sun J
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Chen, Gen
AU  - Chen G
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Niu, Chao
AU  - Niu C
AD  - Pediatric Research Institute, The Second Affiliated Hospital and Yuying 
      Children's Hospital of Wenzhou Medical University, Wenzhou, China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Department of Pharmacy, Jinhua Women & Children Health Hospital, Jinhua, China.
FAU - Zhao, Congcong
AU  - Zhao C
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Sun, Jian
AU  - Sun J
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Huang, Huiya
AU  - Huang H
AD  - Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou 
      Medical University, Wenzhou, China.
FAU - Huang, Shuai
AU  - Huang S
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Liang, Yangzhi
AU  - Liang Y
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Shen, Yingjie
AU  - Shen Y
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Cong, Weitao
AU  - Cong W
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Jin, Litai
AU  - Jin L
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
FAU - Zhu, Zhongxin
AU  - Zhu Z
AD  - School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20190424
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6491521
OTO - NOTNLM
OT  - angiogenesis
OT  - c-Myc
OT  - diabetic wound healing
OT  - endothelial dysfunction
OT  - forkhead box O1
OT  - silent information regulator 1
EDAT- 2019/05/10 06:00
MHDA- 2019/05/10 06:01
PMCR- 2019/04/24
CRDT- 2019/05/10 06:00
PHST- 2019/01/26 00:00 [received]
PHST- 2019/04/03 00:00 [accepted]
PHST- 2019/05/10 06:00 [entrez]
PHST- 2019/05/10 06:00 [pubmed]
PHST- 2019/05/10 06:01 [medline]
PHST- 2019/04/24 00:00 [pmc-release]
AID - 10.3389/fphar.2019.00421 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Apr 24;10:421. doi: 10.3389/fphar.2019.00421. eCollection 
      2019.