PMID- 26993250
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20230411
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Print)
IS  - 0143-5221 (Linking)
VI  - 130
IP  - 11
DP  - 2016 Jun 1
TI  - Mitochondrial function and glucose metabolism in the placenta with gestational 
      diabetes mellitus: role of miR-143.
PG  - 931-41
LID - 10.1042/CS20160076 [doi]
AB  - A predisposing factor for development of the hyperglycaemic state of gestational 
      diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal 
      obesity is associated with significant reductions in placental mitochondrial 
      respiration. MicroRNA (miR)-143 has been previously shown to regulate the 
      metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer 
      tissues. We hypothesized that mitochondrial respiration is reduced and aerobic 
      glycolysis is up-regulated via changes in miR-143 expression in the placenta of 
      women with GDM. Placental tissue was collected at term from women with A1GDM 
      (controlled by diet), A2GDM (controlled by medication) and body mass index 
      (BMI)-matched controls (CTRL). miR-143 expression was measured by RT-PCR. 
      Expression of mitochondrial complexes, transcription factors peroxisome 
      proliferator-activated receptor-gamma co-activator 1alpha (PGC1alpha) and peroxisome 
      proliferator-activated receptor gamma (PPARgamma), components of mammalian target of 
      rapamycin (mTOR) signalling, glucose transporter GLUT1 and glycolytic enzymes 
      [hexokinase-2 (HK-2), phosphofructokinase (PFK) and lactate dehydrogenase (LDH)] 
      were measured by Western blot. Trophoblast respiration was measured by XF24 
      Analyser. Expression of miR-143, mitochondrial complexes, and PPARgamma and PGC1alpha, 
      which act downstream of miR-143, were significantly decreased in A2GDM placentae 
      compared with A1GDM and CTRL (P<0.01). Placental hPL (human placental lactogen) 
      levels, expression of glycolytic enzymes, GLUT1 and mTOR signalling were also 
      significantly increased by more than 2-fold in A2GDM compared with A1GDM and CTRL 
      (P<0.05). There was a 50% reduction in mitochondrial respiration in trophoblast 
      cells isolated from A2GDM placentae. Overexpression of miR-143 was able to 
      increase mitochondrial respiration, increase protein expression of mitochondrial 
      complexes and decrease expression of glycolytic enzymes by 40% compared with 
      A2GDM. Down-regulation of miR-143 mediates the metabolic switch from oxidative 
      phosphorylation to aerobic glycolysis in placenta of women with A2GDM.
CI  - (c) 2016 The Author(s). published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Muralimanoharan, Sribalasubashini
AU  - Muralimanoharan S
AD  - Center for Pregnancy and Newborn Research, Department of Ob/Gyn, University of 
      Texas Health Science Center San Antonio, San Antonio, TX 78229, U.S.A.
FAU - Maloyan, Alina
AU  - Maloyan A
AD  - Center for Pregnancy and Newborn Research, Department of Ob/Gyn, University of 
      Texas Health Science Center San Antonio, San Antonio, TX 78229, U.S.A.
FAU - Myatt, Leslie
AU  - Myatt L
AD  - Center for Pregnancy and Newborn Research, Department of Ob/Gyn, University of 
      Texas Health Science Center San Antonio, San Antonio, TX 78229, U.S.A. 
      myattl@ohsu.edu.
LA  - eng
GR  - R01 HD076259/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160318
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (MIRN143 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Carbohydrate Metabolism/genetics
MH  - Diabetes, Gestational/*genetics
MH  - Female
MH  - Glucose/*metabolism
MH  - Humans
MH  - Hyperglycemia/*genetics/metabolism
MH  - MicroRNAs/*genetics
MH  - Mitochondria/*genetics/metabolism
MH  - Obesity
MH  - Placenta/*metabolism
MH  - Pregnancy
MH  - TOR Serine-Threonine Kinases/genetics
PMC - PMC4918818
MID - NIHMS793527
OTO - NOTNLM
OT  - gestational diabetes
OT  - mammalian target of rapamycin (mTOR)
OT  - miR-143
OT  - mitochondrial function
OT  - placenta
EDAT- 2016/03/20 06:00
MHDA- 2017/04/07 06:00
PMCR- 2016/06/23
CRDT- 2016/03/20 06:00
PHST- 2016/03/03 00:00 [received]
PHST- 2016/03/17 00:00 [accepted]
PHST- 2016/03/20 06:00 [entrez]
PHST- 2016/03/20 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
PHST- 2016/06/23 00:00 [pmc-release]
AID - CS20160076 [pii]
AID - 10.1042/CS20160076 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2016 Jun 1;130(11):931-41. doi: 10.1042/CS20160076. Epub 2016 
      Mar 18.