PMID- 27126232
OWN - NLM
STAT- MEDLINE
DCOM- 20180112
LR  - 20181202
IS  - 1029-2292 (Electronic)
IS  - 0897-7194 (Linking)
VI  - 34
IP  - 1-2
DP  - 2016 Feb
TI  - Glucocorticoids modify effects of TGF-beta1 on multidrug resistance in the fetal 
      blood-brain barrier.
PG  - 33-41
LID - 10.3109/08977194.2016.1162163 [doi]
AB  - Transforming growth factor-beta1 (TGF-beta1) increases P-glycoprotein (P-gp; encoded by 
      Abcb1) activity in fetal brain endothelial cells (BECs). P-gp is important for 
      fetal brain protection against xenobiotics including synthetic glucocorticoids 
      (sGC). We hypothesized that antenatal sGC would modify P-gp responsiveness to 
      TGF-beta1 in fetal BECs. Pregnant guinea pigs were treated with dexamethasone or 
      vehicle (N = 5/group) on gestational day (GD) 48-49 and BECs derived on GD50. In 
      BECs from control fetuses, TGF-beta1 increased Abcb1 mRNA and P-gp function, by 
      approximately 5-fold and 55% respectively, as well as tight junction function. In 
      contrast, TGF-beta1 had no effect on these parameters in BECs from sGC-exposed 
      fetuses. Moreover, levels of TGF-beta1 responsive gene, Smad7, were increased 3-fold 
      in BECs from control fetuses after TGF-beta1 but not in sGC-exposed fetuses. In 
      conclusion, antenatal sGC alters responsiveness to TGF-beta1 in fetal BECs. This 
      study has identified novel mechanisms by which TGF-beta1 and sGC modulate fetal 
      brain protection against xenobiotics and other P-gp substrates.
FAU - Baello, Stephanie
AU  - Baello S
AD  - a Department of Physiology , University of Toronto , Toronto , ON , Canada .
FAU - Iqbal, Majid
AU  - Iqbal M
AD  - a Department of Physiology , University of Toronto , Toronto , ON , Canada .
FAU - Kearney, Samantha
AU  - Kearney S
AD  - a Department of Physiology , University of Toronto , Toronto , ON , Canada .
FAU - Kuthiala, Shikah
AU  - Kuthiala S
AD  - a Department of Physiology , University of Toronto , Toronto , ON , Canada .
FAU - Bloise, Enrrico
AU  - Bloise E
AD  - b Department of Morphology , Federal University of Minas Gerais , Belo Horizonte 
      , Brazil .
FAU - Gibb, William
AU  - Gibb W
AD  - c Department of Obstetrics and Gynecology , and Cellular and Molecular Medicine, 
      University of Ottawa , Ottawa , ON , Canada .
FAU - Matthews, Stephen G
AU  - Matthews SG
AD  - a Department of Physiology , University of Toronto , Toronto , ON , Canada .
AD  - d Department of Obstetrics and Gynecology , University of Toronto , Toronto , ON 
      , Canada , and.
AD  - e Department of Medicine , Faculty of Medicine, University of Toronto , Toronto , 
      ON , Canada.
LA  - eng
GR  - FRN-84220/CIHR/Canada
PT  - Journal Article
DEP - 20160428
PL  - England
TA  - Growth Factors
JT  - Growth factors (Chur, Switzerland)
JID - 9000468
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Smad7 Protein)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism
MH  - Animals
MH  - Blood-Brain Barrier/*drug effects/embryology/metabolism
MH  - Cells, Cultured
MH  - Drug Resistance, Multiple
MH  - Female
MH  - Glucocorticoids/*pharmacology
MH  - Guinea Pigs
MH  - RNA, Messenger/genetics/metabolism
MH  - Smad7 Protein/genetics/metabolism
MH  - Transforming Growth Factor beta1/*pharmacology
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - TGF-beta1
OT  - endothelial cell
OT  - fetus
OT  - multidrug resistance
OT  - prenatal glucocorticoids
EDAT- 2016/04/30 06:00
MHDA- 2018/01/13 06:00
CRDT- 2016/04/30 06:00
PHST- 2016/04/30 06:00 [entrez]
PHST- 2016/04/30 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
AID - 10.3109/08977194.2016.1162163 [doi]
PST - ppublish
SO  - Growth Factors. 2016 Feb;34(1-2):33-41. doi: 10.3109/08977194.2016.1162163. Epub 
      2016 Apr 28.