Vasoinhibin Suppresses the Neurotrophic Effects of VEGF and NGF in Newborn Rat Primary Sensory Neurons

2017 ◽  
Vol 106 (3) ◽  
pp. 221-233 ◽  
Author(s):  
Ximena Castillo ◽  
Zesergio Melo ◽  
Alfredo Varela-Echavarría ◽  
Elisa Tamariz ◽  
Rodrigo M. Aroña ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neurite Outgrowth ◽  
Sensory Neurons ◽  
Target Cells ◽  
Vascular Endothelial ◽  
Primary Sensory Neurons ◽  
Drg Neurons ◽  
Newborn Rat ◽  
Akt Phosphorylation ◽  
Endothelial Growth Factor

Background/Aims: Studies on the biological actions of vasoinhibins have focused mainly on endothelial cells. However, there is incipient knowledge about how vasoinhibins affect the nervous system, even if the target cells and mechanisms of action involved in these effects are unknown. Methods: In order to determine if neurons are direct targets of vasoinhibins, we examined cellular outcomes and the intracellular pathways involved in the neuronal actions of vasoinhibins using newborn rat dorsal root ganglion (DRG) neurons as a model system. Results: Vascular endothelial growth factor (VEGF) or nerve growth factor (NGF) treatment for 48 h resulted in neurite outgrowth stimulation in both DRG cultured explants and isolated primary sensory neurons. Interestingly, a recombinant vasoinhibin containing the first 123 amino acids of human prolactin antagonized the VEGF- and NGF-induced stimulation of neurite outgrowth. Vasoinhibin significantly reduced the density of neurites in DRG explants and obliterated neuritogenesis in isolated DRG neurons in primary culture, supporting a direct neuronal effect of vasoinhibin. In cultures of isolated DRG cells, virtually all β3-tubulin-labeled cells express TrkA, and the majority of these cells also express VEGFR2. Short-term VEGF or NGF treatment of DRG explants resulted in increased ERK1/2 and AKT phosphorylation, whereas incubation of DRG with the combination of either VEGF or NGF together with vasoinhibin resulted in blunted VEGF- or NGF-induced phosphorylation of both ERK1/2 and AKT. Conclusion: Our results show that primary sensory neurons are direct targets of vasoinhibin, and suggest that vasoinhibin inhibition of neurite outgrowth involves the disruption of ERK and AKT phosphorylation cascades.

scholarly journals Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR by estradiol through VEGF in uterus

2006 ◽  
Vol 188 (1) ◽  
pp. 91-99 ◽  
Author(s):  
M A J Hervé ◽  
G Meduri ◽  
F G Petit ◽  
T S Domet ◽  
G Lazennec ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Receptor Expression ◽  
Maximal Response ◽  
Target Cells ◽  
Vegf Receptor ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

The induction of vascular endothelial growth factor (VEGF) expression by 17β-estradiol (E2) in many target cells, including epithelial cells, fibroblasts and smooth muscle cells, suggests a role for this hormone in the modulation of angiogenesis and vascular permeability. We have already described a cyclic increase in Flk-1/KDR-expressing capillaries in the human endometrium during the proliferative and mid-secretory phases, strongly suggestive of an E2 effect on Flk-1/KDR expression in the endometrial capillaries. However, it is unclear whether these processes are due to a direct effect of E2 on endothelial cells. Using immunohistochemistry, we report an increase in Flk-1/KDR expression in endometrial capillaries of ovariectomized mice treated with E2, or both E2 and progesterone. This process is mediated through estrogen receptor (ER) activation. In vitro experiments using quantitative RT-PCR analysis demonstrate that Flk-1/KDR expression was not regulated by E2 in human endothelial cells from the microcirculation (HMEC-1) or macrocirculation (HUVEC), even in endothelial cells overexpressing ERα or ERβ after ER-mediated adenovirus infection. In contrast, Flk-1/KDR expression was up-regulated by VEGF itself, in a time- and dose-dependent manner, with the maximal response at 10 ng/ml. Thus, we suggest that E2 up-regulates Flk-1/KDR expression in vivo in endothelial cells mainly through the modulation of VEGF by a paracrine mechanism. It is currently unknown whether or not the endothelial origin might account for differences in the E2-modulation of VEGF receptor expression, particularly in relation to the vascular bed of sex steroid-responsive tissues.

scholarly journals The Protective Role of Yin‐Yang 1 in Cardiac Injury and Remodeling After Myocardial Infarction

2021 ◽  
Author(s):  
Yu Huang ◽  
Liangpeng Li ◽  
Hongmei Chen ◽  
Qiao Liao ◽  
Xiaoli Yang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cytokine Production ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Vascular Endothelial ◽  
T Helper ◽  
Akt Phosphorylation ◽  
T Helper 2 ◽  
Endothelial Growth Factor

Background Exploring potential therapeutic target is of great significance for myocardial infarction (MI) and post‐MI heart failure. Transcription factor Yin‐Yang 1 (YY1) is an essential regulator of apoptosis and angiogenesis, but its role in MI is unclear. Methods and Results The expression of YY1 was assessed in the C57BL/6J mouse heart following MI. Overexpression or silencing of YY1 in the mouse heart was achieved by adeno‐associated virus 9 injection. The survival, cardiac function, and scar size, as well as the apoptosis, angiogenesis, cardiac fibrosis, T helper 2 lymphocyte cytokine production, and macrophage polarization were assessed. The effects of YY1 on Akt phosphorylation and vascular endothelial growth factor production were also investigated. The expression of YY1 in heart was significantly stimulated by MI. The survival rate, cardiac function, scar size, and left ventricular volume of mice were improved by YY1 overexpression but worsened by YY1 silencing. YY1 alleviated cardiac apoptosis and fibrosis, promoted angiogenesis, T helper 2 cytokine production, and M2 macrophage polarization in the post‐MI heart, it also enhanced the tube formation and migration ability of endothelial cells. Enhanced Akt phosphorylation, along with the increased vascular endothelial growth factor levels were observed in presence of YY1 overexpression. Conclusions YY1 ameliorates cardiac injury and remodeling after MI by repressing cardiomyocyte apoptosis and boosting angiogenesis, which might be ascribed to the enhancement of Akt phosphorylation and the subsequent vascular endothelial growth factor up‐regulation. Increased T helper 2 cytokine production and M2 macrophage polarization may also be involved in YY1’s cardioprotective effects. These findings supported YY1 as a potential target for therapeutic investigation of MI.

scholarly journals Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 953 ◽  
Author(s):  
Manoj Kumar Jena ◽  
Neeta Raj Sharma ◽  
Matthew Petitt ◽  
Devika Maulik ◽  
Nihar Ranjan Nayak
Keyword(s):  
Growth Factor ◽  
Clinical Symptoms ◽  
Growth Factor Receptor ◽  
Target Cells ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Endothelial Growth Factor ◽  
Maternal Disease ◽  
Placental Ischemia

Preeclampsia (PE) is a serious pregnancy complication, affecting about 5–7% of pregnancies worldwide and is characterized by hypertension and damage to multiple maternal organs, primarily the liver and kidneys. PE usually begins after 20 weeks’ gestation and, if left untreated, can lead to serious complications and lifelong disabilities—even death—in both the mother and the infant. As delivery is the only cure for the disease, treatment is primarily focused on the management of blood pressure and other clinical symptoms. The pathogenesis of PE is still not clear. Abnormal spiral artery remodeling, placental ischemia and a resulting increase in the circulating levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also called soluble fms-like tyrosine kinase-1 (sFlt-1), are believed to be among the primary pathologies associated with PE. sFlt-1 is produced mainly in the placenta during pregnancy and acts as a decoy receptor, binding to free VEGF (VEGF-A) and placental growth factor (PlGF), resulting in the decreased bioavailability of each to target cells. Despite the pathogenic effects of increased sFlt-1 on the maternal vasculature, recent studies from our laboratory and others have strongly indicated that the increase in sFlt-1 in PE may fulfill critical protective functions in preeclamptic pregnancies. Thus, further studies on the roles of sFlt-1 in normal and preeclamptic pregnancies are warranted for the development of therapeutic strategies targeting VEGF signaling for the treatment of PE. Another impediment to the treatment of PE is the lack of suitable methods for delivery of cargo to placental cells, as PE is believed to be of placental origin and most available therapies for PE adversely impact both the mother and the fetus. The present review discusses the pathogenesis of PE, the complex role of sFlt-1 in maternal disease and fetal protection, and the recently developed placenta-targeted drug delivery system for the potential treatment of PE with candidate therapeutic agents.

Neurite outgrowth in normal and injured primary sensory neurons reveals different regulation by nerve growth factor (NGF) and artemin

2015 ◽  
Vol 65 ◽  
pp. 125-134 ◽  
Author(s):  
Agnes W. Wong ◽  
James K. P. Yeung ◽  
Sophie C. Payne ◽  
Janet R. Keast ◽  
Peregrine B. Osborne
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurite Outgrowth ◽  
Sensory Neurons ◽  
Primary Sensory Neurons ◽  
Nerve Growth
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