scholarly journals NF-κB contributes to transcription of placenta growth factor and interacts with metal responsive transcription factor-1 in hypoxic human cells

2006 ◽  
Vol 387 (1) ◽  
Author(s):  
Mirjam Cramer ◽  
Ivana Nagy ◽  
Brian J. Murphy ◽  
Max Gassmann ◽  
Michael O. Hottiger ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Human Cells ◽  
Placenta Growth Factor ◽  
Transcription Factor 1

scholarly journals NF-κB contributes to transcription of placenta growth factor and interacts with metal responsive transcription factor-1 in hypoxic human cells

2005 ◽  
Vol 386 (9) ◽  
pp. 865-872 ◽  
Author(s):  
Mirjam Cramer ◽  
Ivana Nagy ◽  
Brian J. Murphy ◽  
Max Gassmann ◽  
Michael O. Hottiger ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Transcription Factor ◽  
Growth Factor ◽  
Nuclear Translocation ◽  
Plasmid Vector ◽  
Hek293 Cells ◽  
Vascular Endothelial ◽  
Placenta Growth Factor ◽  
Endothelial Growth Factor ◽  
Transcription Factor 1

Abstract Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor family of cytokines that control vascular and lymphatic endothelium development. It has been implicated in promoting angiogenesis in pathological conditions via signaling to vascular endothelial growth factor receptor-1. PlGF expression is induced by hypoxia and proinflammatory stimuli. Metal responsive transcription factor 1 (MTF-1) was shown to take part in the hypoxic induction of PlGF in Ras-transformed mouse embryonic fibroblasts. Here we report that PlGF expression is also controlled by NF-κB. We identified several putative binding sites for NF-κB in the PlGF promoter/enhancer region by sequence analyses, and show binding and transcriptional activity of NF-κB p65 at these sites. Expression of NF-κB p65 from a plasmid vector in HEK293 cells caused a substantial increase of PlGF transcript levels. Furthermore, we found that hypoxic conditions induce nuclear translocation and interaction of MTF-1 and NF-κB p65 proteins, suggesting a role for this complex in hypoxia-induced transcription of PlGF.

scholarly journals Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor

Blood ◽  
2014 ◽  
Vol 124 (6) ◽  
pp. 946-954 ◽  
Author(s):  
Xunde Wang ◽  
Laurel Mendelsohn ◽  
Heather Rogers ◽  
Susan Leitman ◽  
Nalini Raghavachari ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Sickle Cell Disease ◽  
Erythroid Cells ◽  
Cell Disease ◽  
Placenta Growth Factor ◽  
Key Points ◽  
Factor Expression ◽  
Growth Factor Expression ◽  
In Erythroid Cells

Key Points Heme-bound iron activates placenta growth factor expression in erythroid cells via EKLF, a crucial erythroid-specific transcription factor. Markers of iron burden predict mortality in adults with sickle cell disease.

scholarly journals Metal Transcription Factor-1 Is Involved in Hypoxia-Dependent Regulation of Placenta Growth Factor in Trophoblast-Derived Cells

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1801-1808 ◽  
Author(s):  
Fumihito Nishimoto ◽  
Masahiro Sakata ◽  
Ryoko Minekawa ◽  
Yoko Okamoto ◽  
Asako Miyake ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Pregnant Women ◽  
Promoter Region ◽  
Small Interfering Rna ◽  
Angiogenic Factor ◽  
Bewo Cell ◽  
Placenta Growth Factor ◽  
Promoter Deletion Analysis ◽  
Interfering Rna

Placenta growth factor (PlGF) is a placental angiogenic factor. Metal-responsive transcription factor (MTF)-1 was reported to take part in the hypoxic induction of PlGF in RAS-transformed mouse fibroblasts. We contrarily showed that PlGF mRNA and protein levels decreased under hypoxia in a choriocarcinoma BeWo cell line derived from trophoblast. In this report, we examined whether hypoxia-dependent regulation of the PlGF gene in these cells also depends on MTF-1. We analyzed the effect of hypoxia on MTF-1 expression, and it was revealed to be decreased. Moreover, MTF-1 small interfering RNA treatment decreased PlGF mRNA level. To investigate the transcription of PlGF under hypoxia, we cloned promoter region of the human PlGF. Promoter deletion analysis suggested that triple repeats of metal-responsive element located between −511 and −468 bp in the promoter are important for the hypoxic regulation of PlGF. Treatment with MTF-1 small interfering RNA resulted in the significant decreased luciferase activity in PlGF reporter constructs. Chromatin immunoprecipitation showed the binding of the MTF-1 protein to the promoter region. We examined MTF-1 immunoreactivity in trophoblasts of term placental tissue from patients with normal pregnancies and preeclampsia, which represents a condition of placental hypoxia. Immunoreactivity of the MTF-1 protein was decreased in placentas from pregnant women with preeclampsia when compared with those from normal pregnant women. Taken together, these findings suggest that MTF-1 is involved in hypoxia-dependent regulation of PlGF in trophoblast-derived cells.

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