کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6280567 | 1615093 | 2015 | 6 صفحه PDF | دانلود رایگان |
- BMP4, BMP7 and BMPRIa were demonstrated in human fetal leptomeninges at multiple ages for the first time.
- BMP7 stimulated 17 and 20Â wk leptomeningeal cell DNA synthesis.
- BMP4 and 7 increased phosphorylation of SMAD 1,4,5 but not p38 MAPK or p44/42MAPK.
- BMP 4 and 7 had no effect on TGF-B precursor or TGFBR1 levels.
- BMP4 and BMP7 increased VEGFR1 RNA in leptomeningeal cultures.
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 17Â wks. Immunohistochemically, BMP4 immunoreactivity was also found in 20 to 39Â wk human leptomeninges.BMP4 significantly reduced basal DNA synthesis at 22Â wks. BMP7 100 and 300Â ng/ml stimulated basal DNA synthesis in the 15, 17 and 22Â 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.
Journal: Neuroscience Letters - Volume 606, 8 October 2015, Pages 225-230