PMID- 36909311
OWN - NLM
STAT- MEDLINE
DCOM- 20230315
LR  - 20231106
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - High glucose induced HIF-1alpha/TREK1 expression and myometrium relaxation during 
      pregnancy.
PG  - 1115619
LID - 10.3389/fendo.2023.1115619 [doi]
LID - 1115619
AB  - BACKGROUND: The incidence of gestational diabetes mellitus (GDM) is increasing 
      worldwide. GDM patients have a significantly higher rate of cesarean section and 
      postpartum hemorrhage, suggesting changes in uterine contractility. 
      TWIK-1-related potassium channel (TREK1) expressed in the pregnant uterus and its 
      role in uterine contraction. In this study, we examined the expression of HIF-1alpha 
      and TREK1 proteins in GDM uterine and investigated whether high glucose levels 
      are involved in the regulation of human uterine smooth muscle cells (HUSMCs) 
      contraction through TREK1, and verified the role of HIF-1alpha in this process. 
      METHODS: Compared the uterine contractility between GDM and normal patients 
      undergoing elective lower segment cesarean section. The HUSMCs were divided into 
      normal glucose group, high glucose group, normal glucose with CoCl2 group, CoCl2 
      with echinomycin/L-Methionine group, and high glucose with 
      echinomycin/L-Methionine group; Compare the cell contractility of each group. 
      Compared the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and TREK1 protein 
      in each group. RESULTS: The contractility of human uterine strips induced by both 
      KCl and oxytocin was significantly lower in patients with GDM compared with that 
      in normal individuals, with increased TREK1 and HIF-1alpha protein expression. The 
      contractility of cultured HUSMCs was significantly decreased under high glucose 
      levels, which was consistent with increased expression of HIF-1alpha and TREK1 
      proteins. The contractility of HUSMCs was decreased when hypoxia was induced by 
      CoCl2 and increased when hypoxia was inhibited by echinomycin. The TREK1 
      inhibitor L-methionine also recovered the decreased contractility of HUSMCs under 
      high glucose levels or hypoxia. DISCUSSION: The high glucose levels decreased the 
      contractility of the myometrium, and increased expression of HIF-1a and TREK1 
      proteins play a role in changes in uterus contractility.
CI  - Copyright (c) 2023 Li, Fei, Yu, Wang, Bai, Chen, Li and Yin.
FAU - Li, Tengteng
AU  - Li T
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
AD  - Department of Obstetrics and Gynecology, Chaohu Hospital of Anhui Medical 
      University, Chaohu, China.
FAU - Fei, Jiajia
AU  - Fei J
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Yu, Huihui
AU  - Yu H
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Wang, Xingxing
AU  - Wang X
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Bai, Jingjing
AU  - Bai J
AD  - Department of Obstetrics and Gynecology, Chaohu Hospital of Anhui Medical 
      University, Chaohu, China.
FAU - Chen, Fucai
AU  - Chen F
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Li, Dan
AU  - Li D
AD  - Department of Scientific Research, The Second Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
FAU - Yin, Zongzhi
AU  - Yin Z
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui 
      Medical University, Hefei, China.
AD  - Department of Obstetrics and Gynecology, Chaohu Hospital of Anhui Medical 
      University, Chaohu, China.
AD  - National Health Commission (NHC) Key Laboratory of the Study of Abnormal Gametes 
      and the Reproductive Tract, Anhui Medical University, Hefei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230227
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 3G0H8C9362 (Cobalt)
RN  - 512-64-1 (Echinomycin)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - AE28F7PNPL (Methionine)
RN  - 0 (HIF1A protein, human)
RN  - 0 (potassium channel protein TREK-1)
SB  - IM
EIN - Front Endocrinol (Lausanne). 2023 Apr 13;14:1200774. PMID: 37124756
MH  - Female
MH  - Humans
MH  - Pregnancy
MH  - Cesarean Section
MH  - Cobalt/metabolism
MH  - *Echinomycin/metabolism
MH  - Glucose/metabolism
MH  - Hypoxia/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Methionine/metabolism
MH  - *Myometrium
PMC - PMC9998977
OTO - NOTNLM
OT  - HIF-1alpha
OT  - TREK1
OT  - gestational diabetes mellitus
OT  - human uterine smooth muscle cells
OT  - myometrium contractility
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- 2023/03/14 06:00
MHDA- 2023/03/15 06:00
PMCR- 2023/01/01
CRDT- 2023/03/13 03:58
PHST- 2022/12/04 00:00 [received]
PHST- 2023/02/13 00:00 [accepted]
PHST- 2023/03/13 03:58 [entrez]
PHST- 2023/03/14 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.1115619 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2023 Feb 27;14:1115619. doi: 
      10.3389/fendo.2023.1115619. eCollection 2023.