scholarly journals Regulation of Pancreatic α-Cell Function and Proliferation by Bone Morphogenetic Protein 4 (BMP4) In Vitro

Endocrinology ◽  
2016 ◽  
Vol 157 (10) ◽  
pp. 3809-3820 ◽  
Author(s):  
Sofie Sylvest Nielsen ◽  
Gitte Lund Christensen ◽  
Jens Juul Holst ◽  
Nils Billestrup
Keyword(s):  
Bone Morphogenetic Protein ◽  
Cell Function ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein

scholarly journals Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development.

1995 ◽  
Vol 15 (1) ◽  
pp. 141-151 ◽  
Author(s):  
B M Johansson ◽  
M V Wiles
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Protein ◽  
Activin A ◽  
Bone Morphogenetic Protein 4 ◽  
Mesoderm Induction ◽  
Dependent Manner ◽  
Tgf Beta ◽  
Mouse Development ◽  
Morphogenetic Protein

Xenopus in vitro studies have implicated both transforming growth factor beta (TGF-beta) and fibroblast growth factor (FGF) families in mesoderm induction. Although members of both families are present during mouse mesoderm formation, there is little evidence for their functional role in mesoderm induction. We show that mouse embryonic stem cells, which resemble primitive ectoderm, can differentiate to mesoderm in vitro in a chemically defined medium (CDM) in the absence of fetal bovine serum. In CDM, this differentiation is responsive to TGF-beta family members in a concentration-dependent manner, with activin A mediating the formation of dorsoanterior-like mesoderm and bone morphogenetic protein 4 mediating the formation of ventral mesoderm, including hematopoietic precursors. These effects are not observed in CDM alone or when TGF-beta 1, -beta 2, or -beta 3, acid FGF, or basic FGF is added individually to CDM. In vivo, at day 6.5 of mouse development, activin beta A RNA is detectable in the decidua and bone morphogenetic protein 4 RNA is detectable in the egg cylinder. Together, our data strongly implicate the TGF-beta family in mammalian mesoderm development and hematopoietic cell formation.

scholarly journals Stimulation of Epithelial Sodium Channels in Endothelial Cells by Bone Morphogenetic Protein-4 Contributes to Salt-Sensitive Hypertension in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xu Yang ◽  
Na Niu ◽  
Chen Liang ◽  
Ming-Ming Wu ◽  
Liang-Liang Tang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Bone Morphogenetic Protein ◽  
Salt Intake ◽  
High Salt ◽  
Bone Morphogenetic Protein 4 ◽  
Sodium Influx ◽  
Morphogenetic Protein ◽  
High Salt Intake ◽  
Stimulation Of

Previous studies have shown that high salt induces artery stiffness by causing endothelial dysfunction via increased sodium influx. We used our unique split-open artery technique combined with protein biochemistry and in vitro measurement of vascular tone to test a hypothesis that bone morphogenetic protein 4 (BMP4) mediates high salt-induced loss of vascular relaxation by stimulating the epithelial sodium channel (ENaC) in endothelial cells. The data show that high salt intake increased BMP4 both in endothelial cells and in the serum and that exogenous BMP4 stimulated ENaC in endothelial cells. The data also show that the stimulation is mediated by p38 mitogen-activated protein kinases (p38 MAPK) and serum and glucocorticoid-regulated kinase 1 (Sgk1)/neural precursor cell expressed developmentally downregulated gene 4-2 (Nedd4-2) (Sgk1/Nedd4-2). Furthermore, BMP4 decreased mesenteric artery relaxation in a benzamil-sensitive manner. These results suggest that high salt intake stimulates endothelial cells to express and release BMP4 and that the released BMP4 reduces artery relaxation by stimulating ENaC in endothelial cells. Therefore, stimulation of ENaC in endothelial cells by BMP4 may serve as another pathway to participate in the complex mechanism of salt-sensitive (SS) hypertension.

Bone morphogenetic protein 4 regulates microRNAs miR-494 and miR-126–5p in control of endothelial cell function in angiogenesis

2017 ◽  
Vol 117 (04) ◽  
pp. 734-749 ◽  
Author(s):  
Erika Saretzki ◽  
Franziska Pankratz ◽  
Bianca Engert ◽  
Sebastian Grundmann ◽  
Christoph Bode ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Western Blot ◽  
Bone Morphogenetic Protein ◽  
Cell Function ◽  
Umbilical Vein ◽  
Endothelial Cell Proliferation ◽  
Bone Morphogenetic Protein 4 ◽  
Endothelial Cell Function ◽  
Morphogenetic Protein

SummaryMicroRNAs are small non-coding RNAs that negatively regulate posttranscriptional gene expression. Several microRNAs have been described to regulate the process of angiogenesis. Previously, we have shown that bone morphogenetic protein 4 (BMP4) increased the proangiogenic activity of endothelial cells. In this project, we now investigated how the pro-angiogenic BMP4 effect is mediated by microRNAs. First, we performed a microRNA array with BMP4-stimulated human umbilical vein endothelial cells (HUVECs). Among the topregulated microRNAs, we detected a decreased expression of miR-494 and increased expression of miR-126–5p. Next, we analysed the canonical Smad and alternative signalling pathways, through which BMP4 would regulate miR-126–5p and miR-494 expression. Furthermore, the functional effect of miR-494 and miR-126–5p on endothelial cells was investigated. MicroRNA-494 overexpression decreased endothelial cell proliferation, migration and sprout formation. Consistently, miR-494 inhibition increased endothelial cell function. As potential miR-494 targets, bFGF and BMP endothelial cell precursorderived regulator (BMPER) were identified and confirmed by western blot. Luciferase assays showed direct miR-494 binding in BMPER 3’UTR. In contrast, miR-126–5p overexpression increased pro-angiogenic endothelial cell behaviour and, accordingly, miR-126–5p inhibition decreased endothelial cell function. As a direct miR-126–5p target we identified the anti-angiogenic thrombospondin-1 which was confirmed by western blot analysis and luciferase assays. In the Matrigel plug assay application of antagomiR-494 increased endothelial cell ingrowth, whereas antagomiR-126–5p treatment decreased cell ingrowth in vivo. Taken together, through differential regulation of the anti-angiomiR-494 and the angiomiR-126–5p by BMP4 both microRNAs contribute to the pro-angiogenic BMP4 effect on endothelial cells.Supplementary Material to this article is available online at www.thrombosis-online.com.

Bone morphogenetic protein 4 induces efficient hematopoietic differentiation of rhesus monkey embryonic stem cells in vitro

Blood ◽  
2001 ◽  
Vol 98 (2) ◽  
pp. 335-342 ◽  
Author(s):  
Fei Li ◽  
Shijiang Lu ◽  
Loyda Vida ◽  
James A. Thomson ◽  
George R. Honig
Keyword(s):  
Rhesus Monkey ◽  
Bone Morphogenetic Protein ◽  
Culture System ◽  
Es Cells ◽  
Regulatory Protein ◽  
Embryonic Stem ◽  
Bone Morphogenetic Protein 4 ◽  
Hematopoietic Differentiation ◽  
Morphogenetic Protein

A cell culture system consisting of mouse S17 stromal cells supplemented with cytokines was developed for hematopoietic differentiation of rhesus monkey embryonic stem (ES) cells. The differentiated colonies that formed contained clusters of hematopoietic-like cells, as well as structures similar in appearance to embryonic blood islands. When this culture system was supplemented with bone morphogenetic protein 4 (BMP-4), the numbers of primary hematopoietic clusters increased by an average of 15 fold. The primary hematopoietic clusters containing clonogenic precursors (expandable hematopoietic clusters) increased by 18 fold. Immunofluorescence analysis showed that a substantial percentage of the hematopoietic-like cells were CD34+, with morphologic features of undifferentiated blast cells. Enrichment of the CD34+ cells was associated with enhanced stromal-dependent, cytokine-driven formation of cobblestone colonies on secondary plating. The hematopoietic identity of the precursors was further indicated by their expression of genes associated with hematopoietic differentiation, as well as morphologic assessments that showed erythroid and myeloid lineages among the progeny cells. In addition, reverse transcriptase–polymerase chain reaction analysis of BMP-4–treated rhesus monkey ES cells demonstrated an up-regulation of early-expressed genes responsible for embryonic hematopoiesis and angiogenesis during the first 7 days of culture. These observations suggest that embryonic mesoderm regulatory protein may mimic physiologic signals that are required for the onset of embryonic hematopoiesis and stem cell formation in rhesus monkey ES cells.

Sign in / Sign up

Export Citation Format

Share Document