scholarly journals Ischemia Induces the Expression of the Platelet-Derived Growth Factor-B Chain in Neurons and Brain Macrophages in vivo

1994 ◽  
Vol 14 (5) ◽  
pp. 818-824 ◽  
Author(s):  
Koji Iihara ◽  
Masakiyo Sasahara ◽  
Nobuo Hashimoto ◽  
Yoshihiko Uemura ◽  
Haruhiko Kikuchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Healing Process ◽  
Focal Ischemia ◽  
Platelet Derived Growth Factor ◽  
Northern Analysis ◽  
Brain Macrophages ◽  
Tandem Occlusion ◽  
The Brain

To elucidate the role of the platelet-derived growth factor (PDGF)–B chain in the brain, we examined its expression in rat brains with focal ischemia. Focal ischemia was induced by permanent tandem occlusion of the middle cerebral and common carotid arteries in spontaneously hypertensive rats (SHRs). Northern analysis demonstrated that ischemia transiently increased mRNA expression of the PDGF–B chain, but not the PDGF–A chain, in the injured neocortex. The larger transcript (3.5 kb) of the B chain gradually increased to threefold by 16 h, whereas the smaller transcript (2.6 kb) of the B chain markedly increased sixfold by 4 h. Immunohistochemistry revealed enhanced immunoreactivity in the neurons in the infarct and in the periinfarct area from 16 h to days 4–7, with a peak at 24 h. Furthermore, the brain macrophages that accumulated in the infarct showed intense immunostaining in their perinuclear region from days 2 to 14, with a peak at days 5–6. The present study demonstrates that ischemia induces the expression of the PDGF–B chain, first in neurons and later in brain macrophages, and suggests an important role of the PDGF–B chain in the healing process of the injured brain.

scholarly journals Induction of Platelet-Derived Growth Factor β-Receptor in Focal Ischemia of Rat Brain

1996 ◽  
Vol 16 (5) ◽  
pp. 941-949 ◽  
Author(s):  
Koji Iihara ◽  
Masakiyo Sasahara ◽  
Nobuo Hashimoto ◽  
Fumitada Hazama
Keyword(s):  
Growth Factor ◽  
Rat Brain ◽  
Molecular Layer ◽  
Focal Ischemia ◽  
Platelet Derived Growth Factor ◽  
Northern Analysis ◽  
Ischemic Brain ◽  
Spontaneously Hypertensive ◽  
Tandem Occlusion ◽  
Β Receptor

Our previous study on the ischemia-induced expression of platelet-derived growth factor (PDGF)-B chain in the rat brain prompted us to examine expression of PDGF β-receptor in the ischemic brain. Focal ischemia was induced by permanent tandem occlusion of middle cerebral and common carotid arteries in spontaneously hypertensive rats. Northern analysis revealed that ischemia significantly increased expression of the receptor in the ischemic neocortex at 4 and 7 days (328 ± 109%; 323 ± 119%, respectively, over control: n = 4, p < 0.05 versus sham). Neurons in infarct transiently snowed increased immunostaining for the receptor at 1 day, whereas neurons in periinfarct area showed sustained and increased immunoreactivity from 1 to 14 days postischemia. Reactive glial cells in the external capsule and in molecular layer of the neocortex adjacent to infarct possessed enhanced immunoreactivity from 1 to 21 days. Furthermore, marked immunoreactivity was observed on brain macrophages in infarct and on the abluminal side of capillaries surrounding infarct from 4 to 7 days. These results demonstrated that ischemic insult increases expression of the PDGF β-receptor at both the mRNA and protein level in the brain, suggesting its important role in cellular cascade of the ischemic brain.

Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor

1999 ◽  
Vol 79 (4) ◽  
pp. 1283-1316 ◽  
Author(s):  
Carl-Henrik Heldin ◽  
Bengt Westermark
Keyword(s):  
Growth Factor ◽  
Protein Tyrosine Kinase ◽  
Growth Stimulation ◽  
Receptor Activation ◽  
Platelet Derived Growth Factor ◽  
Cellular Effects ◽  
Structural And Functional Properties ◽  
Stimulation Of

Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells and certain other cell types. It is a dimeric molecule consisting of disulfide-bonded, structurally similar A- and B-polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms exert their cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors, denoted the α-receptor and the β-receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the actin filament system and stimulates chemotaxis, i.e., a directed cell movement toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactivity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecule. Similarly, overproduction of PDGF may be involved in autocrine and paracrine growth stimulation of human tumors. Overactivity of PDGF has, in addition, been implicated in nonmalignant conditions characterized by an increased cell proliferation, such as atherosclerosis and fibrotic conditions. This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues.

PDGF signalling is required for gastrulation of Xenopus laevis

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 3099-3110 ◽  
Author(s):  
P. Ataliotis ◽  
K. Symes ◽  
M.M. Chou ◽  
L. Ho ◽  
M. Mercola
Keyword(s):  
Growth Factor ◽  
Marginal Zone ◽  
Platelet Derived Growth Factor ◽  
Pdgf Receptor ◽  
Convergent Extension ◽  
Mesodermal Cell ◽  
Point Mutant ◽  
Receptor Alpha

During Xenopus gastrulation, platelet-derived growth factor (PDGF) receptor-alpha is expressed in involuting marginal zone cells which migrate over ectodermal cells expressing PDGF-A. To investigate the role of PDGF signalling during this process, we have generated a novel point mutant of PDGF receptor-alpha analogous to the W37 mutation of c-kit. This molecule is a specific, potent, dominant inhibitor of PDGF signalling in vivo. Injection of RNA encoding this protein into Xenopus embryos prevents closure of the blastopore, leads to abnormal gastrulation and a loss of anterior structures. Convergent extension is not inhibited in these embryos, but rather, involuting mesodermal cells fail to adhere to the overlying ectoderm. PDGF may therefore be required for mesodermal cell-substratum interaction.

scholarly journals Hyperglycaemia up-regulates placental growth factor (PlGF) expression and secretion in endothelial cells via suppression of PI3 kinase-Akt signalling and activation of FOXO1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samir Sissaoui ◽  
Stuart Egginton ◽  
Ling Ting ◽  
Asif Ahmed ◽  
Peter W. Hewett
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Akt Activation ◽  
Forkhead Box ◽  
Pi3k Activity ◽  
Binding Sequence

AbstractPlacenta growth factor (PlGF) is a pro-inflammatory angiogenic mediator that promotes many pathologies including diabetic complications and atherosclerosis. Widespread endothelial dysfunction precedes the onset of these conditions. As very little is known of the mechanism(s) controlling PlGF expression in pathology we investigated the role of hyperglycaemia in the regulation of PlGF production in endothelial cells. Hyperglycaemia stimulated PlGF secretion in cultured primary endothelial cells, which was suppressed by IGF-1-mediated PI3K/Akt activation. Inhibition of PI3K activity resulted in significant PlGF mRNA up-regulation and protein secretion. Similarly, loss or inhibition of Akt activity significantly increased basal PlGF expression and prevented any further PlGF secretion in hyperglycaemia. Conversely, constitutive Akt activation blocked PlGF secretion irrespective of upstream PI3K activity demonstrating that Akt is a central regulator of PlGF expression. Knock-down of the Forkhead box O-1 (FOXO1) transcription factor, which is negatively regulated by Akt, suppressed both basal and hyperglycaemia-induced PlGF secretion, whilst FOXO1 gain-of-function up-regulated PlGF in vitro and in vivo. FOXO1 association to a FOXO binding sequence identified in the PlGF promoter also increased in hyperglycaemia. This study identifies the PI3K/Akt/FOXO1 signalling axis as a key regulator of PlGF expression and unifying pathway by which PlGF may contribute to common disorders characterised by endothelial dysfunction, providing a target for therapy.

scholarly journals Role of vascular endothelial growth factor in inducing production of angiopoetin-1 – in vivo study in Fisher rats

2017 ◽  
Vol 68 (4) ◽  
pp. 326-329
Author(s):  
Piotr Barć ◽  
Tomasz Płonek ◽  
Dagmara Baczyńska ◽  
Artur Pupka ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
In Vivo Study ◽  
Vascular Endothelial ◽  
Angiopoetin 1 ◽  
Endothelial Growth Factor
Sign in / Sign up

Export Citation Format

Share Document