PMID- 36692102
OWN - NLM
STAT- MEDLINE
DCOM- 20230520
LR  - 20230614
IS  - 1464-5491 (Electronic)
IS  - 0742-3071 (Linking)
VI  - 40
IP  - 6
DP  - 2023 Jun
TI  - Identification of signalling downstream of the transcription factor forkhead box 
      protein M1 that protects against endoplasmic reticulum stress in a diabetic foot 
      ulcer model.
PG  - e15051
LID - 10.1111/dme.15051 [doi]
AB  - AIMS: Diabetic foot ulcer (DFU) has a significant impact on the quality of life 
      of diabetic mellitus (DM) patients. Here, we aimed to explore the molecules with 
      aberrant expression and their regulatory mechanisms in DFU. METHODS: The 
      expression of gene and protein was examined using quantitative polymerase chain 
      reaction (qPCR) and western blot. Pearson's correlation analysis was used to 
      analyse interactions among FOXM1, GAS5 and SDF4. Immunofluorescence was used to 
      detect PDI and GRP78 expression. Flow cytometry was used to assess cell 
      apoptosis. Tube formation assay was used to determine angiogenic capacity. 
      Fluorescence in situ hybridization (FISH) assay was employed to determine the 
      cellular localization of GAS5 and SDF4 in human umbilical vein endothelial cells 
      (HUVECs). The interactions among FOXM1, GAS5 and SDF4 were validated by chromatin 
      immunoprecipitation (ChIP), luciferase, RNA pull-down and RNA immunoprecipitation 
      (RIP) assays. RESULTS: FOXM1, GAS5 and SDF4 were decreased in the skin tissues of 
      DFU patients. High glucose (HG) stimulation induced endoplasmic reticulum (ER) 
      stress and cell apoptosis but suppressed angiogenesis in HUVECs, which were 
      abolished by FOXM1 overexpression. FOXM1 promoted GAS5 transcriptional activity, 
      resulting in increased GAS5 expression, and GAS5 knockdown reversed the effects 
      of FOXM1 overexpression in HG-treated HUVECs. Moreover, GAS5 recruited TAF15 to 
      promote SDF4 expression in HUVECs. GAS5 overexpression inhibited ER stress, cell 
      apoptosis and induced angiogenesis in HG-treated HUVECs which could be reversed 
      by silencing SDF4. CONCLUSION: Our results revealed that FOXM1 suppressed ER 
      stress, cell apoptosis and promoted angiogenesis in HG-induced HUVECs via 
      mediating GAS5/TAF15/SDF4 axis, providing a novel therapeutic molecule mechanism 
      for DFU.
CI  - (c) 2023 Diabetes UK.
FAU - Peng, Weixia
AU  - Peng W
AD  - Department of Endocrine, Yiyang Central Hospital, Yiyang, Hunan, P.R. China.
FAU - Zhu, Ting
AU  - Zhu T
AD  - Department of Endocrine, Yiyang Central Hospital, Yiyang, Hunan, P.R. China.
FAU - Xiang, Guangda
AU  - Xiang G
AD  - Department of Endocrine, Central Theater General Hospital of PLA, Wuhan, Hubei, 
      P.R. China.
FAU - Ding, Ting
AU  - Ding T
AD  - Department of Endocrine, Yiyang Central Hospital, Yiyang, Hunan, P.R. China.
FAU - Zhao, Jun
AU  - Zhao J
AD  - Department of Endocrine, Yiyang Central Hospital, Yiyang, Hunan, P.R. China.
FAU - Xiong, Dan
AU  - Xiong D
AD  - Department of Endocrine, Yiyang Central Hospital, Yiyang, Hunan, P.R. China.
FAU - Zhong, Yaqin
AU  - Zhong Y
AD  - Department of Endocrine, Yiyang Central Hospital, Yiyang, Hunan, P.R. China.
FAU - Zhang, Youqi
AU  - Zhang Y
AUID- ORCID: 0000-0003-4603-4866
AD  - Department of Emergency, Yiyang Central Hospital, Yiyang, Hunan, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230215
PL  - England
TA  - Diabet Med
JT  - Diabetic medicine : a journal of the British Diabetic Association
JID - 8500858
RN  - 0 (Forkhead Box Protein M1)
RN  - 63231-63-0 (RNA)
RN  - 0 (FOXM1 protein, human)
SB  - IM
MH  - Humans
MH  - Apoptosis
MH  - *Diabetes Mellitus/metabolism
MH  - *Diabetic Foot/therapy
MH  - Endoplasmic Reticulum Stress
MH  - Forkhead Box Protein M1/genetics/metabolism/pharmacology
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Quality of Life
MH  - RNA
OTO - NOTNLM
OT  - DFU
OT  - ER stress
OT  - FOXM1
OT  - GAS5
OT  - SDF4
OT  - TAF15
EDAT- 2023/01/25 06:00
MHDA- 2023/05/19 06:42
CRDT- 2023/01/24 07:23
PHST- 2023/01/12 00:00 [revised]
PHST- 2022/09/20 00:00 [received]
PHST- 2023/01/18 00:00 [accepted]
PHST- 2023/05/19 06:42 [medline]
PHST- 2023/01/25 06:00 [pubmed]
PHST- 2023/01/24 07:23 [entrez]
AID - 10.1111/dme.15051 [doi]
PST - ppublish
SO  - Diabet Med. 2023 Jun;40(6):e15051. doi: 10.1111/dme.15051. Epub 2023 Feb 15.