Bone morphogenetic protein-4 and 7 and receptors regulate vascular endothelial growth factor and receptors in human fetal leptomeninges

Mahlon Johnson, Jay E. Reeder, Mary O'Connell

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Bone morphogenetic proteins (BMP) 4 and 7 have important roles in neuronal differentiation and cortical development in the murine brain. However BMP4 and BMP7 expression and functions in the developing human brain are unknown. In this study, frozen tissue human fetal leptomeninges, formalin-fixed tissue and primary fetal leptomeningeal cell cultures were studied. By western blot, BMP4, BMP7 and BMPRIa were demonstrated in 15, 17 20, 23 week (wk) human leptomeninges. BMP receptor II was detected at 15 and 17 wks. Immunohistochemically, BMP4 immunoreactivity was also found in 20 to 39 wk human leptomeninges. BMP4 significantly reduced basal DNA synthesis at 22 wks. BMP7 100 and 300 ng/ml stimulated basal DNA synthesis in the 15, 17 and 22 wk leptomeninges. BMP4 and BMP7 increased phosphorylation of SMAD-1, 5, 8 in most cells and had no effect on phosphorylation of p-38MAPK, or p44/42MAPK. BMP4 and BMP7 produced a decrease in VEGF RNA expression in 2 of 4 leptomeninges. BMP4 and BMP7 increased VEGFR1 RNA in 2 or 3 of 4 leptomeningeal cultures respectively. BMP4 produced a decrease in VEGFR2 RNA in 2 of 4 and BMP7 in 3 of 4 while BMP7 reduced VEGFR2 protein in the leptomeninges. The findings show, for the first time, BMP4, BMP7 and receptors are expressed and active in the human fetal leptomeninges. They suggest these BMPs influence vascular development in this tissue by regulating VEGF and its receptors.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalNeuroscience Letters
Volume606
DOIs
StatePublished - Oct 8 2015
Externally publishedYes

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Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 7
RNA
Fetus
Type II Bone Morphogenetic Protein Receptors
Phosphorylation
Vascular Endothelial Growth Factor Receptor
DNA
Brain
Formaldehyde
Vascular Endothelial Growth Factor A
Blood Vessels
Cell Culture Techniques
Western Blotting
human FLT1 protein
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Bone morphogenetic protein-4 and 7 and receptors regulate vascular endothelial growth factor and receptors in human fetal leptomeninges. / Johnson, Mahlon; Reeder, Jay E.; O'Connell, Mary.

In: Neuroscience Letters, Vol. 606, 08.10.2015, p. 225-230.

Research output: Contribution to journalArticle

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