PMID- 28974422
OWN - NLM
STAT- MEDLINE
DCOM- 20171027
LR  - 20200313
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 493
IP  - 3
DP  - 2017 Nov 25
TI  - Thyroid hormone regulates fibronectin expression through the activation of the 
      hypoxia inducible factor 1.
PG  - 1304-1310
LID - S0006-291X(17)31959-9 [pii]
LID - 10.1016/j.bbrc.2017.09.169 [doi]
AB  - Thyroid hormones regulate gene expression via both canonical and non-canonical 
      signaling. Hyperthyroidism is associated with elevated plasma levels of 
      fibronectin (FN): in this study we elucidate the molecular mechanism through 
      which triiodothyronine (T3) regulates FN and demonstrate that T3 induces FN 
      expression via a non-canonical pathway by activating hypoxia-inducible factor-1 
      (HIF-1). We found that T3 treatment increased cellular and secreted FN in human 
      hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 
      pathway. The inhibition of either Akt phosphorylation with wortmannin or HIF-1 
      with YC1 in both cell types prevented HIF-1alpha synthesis and FN positive regulation 
      upon T3 treatment. We showed that HIF-1alpha overexpression per se was sufficient to 
      up-regulate FN in both cell lines as demonstrated by the transient transfection 
      of both the constitutively active and wild-type forms of HIF-1alpha. Our data 
      demonstrate the involvement of the PI3K/Akt/HIF-1 pathway in mediating T3 induced 
      FN up-regulation.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Taglieri, Ludovica
AU  - Taglieri L
AD  - Department of Experimental Medicine, Sapienza University, Rome, Italy.
FAU - Nardo, Tiziana
AU  - Nardo T
AD  - Department of Experimental Medicine, Sapienza University, Rome, Italy.
FAU - Vicinanza, Roberto
AU  - Vicinanza R
AD  - Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Studies, 
      Sapienza University, Rome, Italy.
FAU - Ross, Jaime M
AU  - Ross JM
AD  - Department of Genetics, Harvard Medical School, Boston, MA, USA; Department of 
      Neuroscience, Karolinska Institutet, Retzius Vag 8, 171 77 Stockholm, Sweden.
FAU - Scarpa, Susanna
AU  - Scarpa S
AD  - Department of Experimental Medicine, Sapienza University, Rome, Italy. Electronic 
      address: susanna.scarpa@uniroma1.it.
FAU - Coppotelli, Giuseppe
AU  - Coppotelli G
AD  - Department of Genetics, Harvard Medical School, Boston, MA, USA. Electronic 
      address: giuseppe_coppotelli@hms.harvard.edu.
LA  - eng
GR  - K99 AG055683/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20170930
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Androstadienes)
RN  - 0 (Fibronectins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Fibroblasts/drug effects/metabolism
MH  - Fibronectins/genetics/*metabolism
MH  - Hep G2 Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - Triiodothyronine/*metabolism/pharmacology
MH  - Wortmannin
OTO - NOTNLM
OT  - Akt
OT  - Fibroblasts
OT  - Fibronectin
OT  - HIF-1
OT  - Hepatoma cells
OT  - T3
EDAT- 2017/10/05 06:00
MHDA- 2017/10/28 06:00
CRDT- 2017/10/05 06:00
PHST- 2017/09/18 00:00 [received]
PHST- 2017/09/30 00:00 [accepted]
PHST- 2017/10/05 06:00 [pubmed]
PHST- 2017/10/28 06:00 [medline]
PHST- 2017/10/05 06:00 [entrez]
AID - S0006-291X(17)31959-9 [pii]
AID - 10.1016/j.bbrc.2017.09.169 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Nov 25;493(3):1304-1310. doi: 
      10.1016/j.bbrc.2017.09.169. Epub 2017 Sep 30.