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Growth Factor Signaling (growth + factor_signaling)
Terms modified by Growth Factor Signaling Selected AbstractsCholesterol Feeding Reduces Vascular Endothelial Growth Factor Signaling in Rabbit Corporal TissuesTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2005Donghua Xie MD ABSTRACT Purpose., Hypercholesterolemia is a major risk factor for erectile dysfunction (ED), but the mechanisms are not completely understood. Vascular endothelial growth factor (VEGF) is reduced in rabbit corporal tissue with cholesterol feeding. VEGF signaling leads to the phosphorylation of Akt and endothelial nitric oxide synthase (p-Akt and p-eNOS). Material and Methods., New Zealand White rabbits (n = 50) were fed a 1% cholesterol (n = 8, 8, 8, 4) or normal (n = 6, 6, 6, 4) diet for 2, 4.5, 7.5, and 12 weeks. Akt, p-Akt, and p-Akt/Akt were measured by enzyme-linked immunosorbent assay. Levels of eNOS, p-eNOS, and neuronal and inducible nitric oxide synthase (nNOS and iNOS) mRNA and protein were assessed by polymerase chain reaction and Western analysis. Results., Cholesterol feeding was associated with a significant decrease in p-Akt/Akt 2.16-fold (P < 0.05), 3.28-fold (P < 0.02), and 3.42-fold (P < 0.02) at 4.5, 7.5, and 12 weeks., respectively. The reduction in p-Akt/Akt with the cholesterol diet at 2 weeks was not significantly different, but the correlation between the duration of cholesterol feeding and the reduction in p-Akt/Akt was high (r,2 = 0.858). eNOS protein or mRNA did not change with cholesterol feeding, but p-eNOS was significantly decreased at 4.5 weeks and all subsequent time points. nNOS mRNA and protein levels were decreased at 4.5 weeks and all subsequent time points, while iNOS was not different between groups. Conclusions., Hypercholesterolemia results in decreased VEGF signaling and decreased levels of the active form of eNOS in corporal tissue. Levels of nNOS were reduced by a different mechanism. VEGF signaling may provide a target to modulate ED. Xie D, Kontos CD, Donatucci CF, and Annex BH. Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues. J Sex Med 2005;2:634,640. [source] Developmental expression of Smoc1 and Smoc2 suggests potential roles in fetal gonad and reproductive tract differentiationDEVELOPMENTAL DYNAMICS, Issue 11 2009Dorothy E. Pazin Abstract SMOC1 and SMOC2 are matricellular proteins thought to influence growth factor signaling, migration, proliferation, and angiogenesis. We examined the expression and regulation of Smoc1 and Smoc2 in fetal gonad/mesonephros complexes to discover possible roles for these genes in gonad and mesonephros development. Smoc1 was upregulated at ,E10.75 in a center-to-poles wave in pre-Sertoli and pre-granulosa cells and its expression was greatly reduced in Wt1, Sf1, and Fog2 mutants. After E13.5, Smoc1 was downregulated in an anterior-to-posterior wave in granulosa cells but persisted in Sertoli cells, suggesting a sexually dimorphic requirement in supporting cell lineage differentiation. Smoc2 was expressed in Leydig cells, mesonephroi, and Wnt4 mutant ovaries, but not wildtype ovaries. Using organ culture, we determined that Smoc2 expression was dependent on Hedgehog signaling in testes, mesonephroi, and kidneys. Overall, these results demonstrate that SMOC1 and SMOC2 may mediate intercellular signaling and cell type,specific differentiation during gonad and reproductive tract development. Developmental Dynamics 238:2877,2890, 2009. © 2009 Wiley-Liss, Inc. [source] Folding of the tectal cortex by local remodeling of neural differentiationDEVELOPMENTAL DYNAMICS, Issue 3 2004Tatsuo Mima Abstract The folding pattern of the brain cortex is a precisely regulated process, but the mechanism involved during development remains unclear. A proposed theory predicts that the initiation of cortical folding depends, at least partly, on nonuniform distribution of neuronal differentiation and neurite growth. We tested this theory experimentally, by remodeling the normal pattern of neuronal cell differentiation within the embryonic optic tectum. Multiple foci of activated fibroblast growth factor signaling were created in the tectal cortex to locally change the neural differentiation and axonal growth patterns. At these foci, tectal cells remained undifferentiated and their radial and tangential migration was suppressed. These local changes in the neuronal cell differentiation resulted in a conversion of the tectal cortex from smoothly extended into precociously folded. The results provide in vivo experimental evidence that microscopic changes in the neuronal cell differentiation pattern can induce or remodel the folding pattern of the brain cortex. Developmental Dynamics 229:475,479, 2004. © 2004 Wiley-Liss, Inc. [source] Ontogeny of energy homeostatic pathways via neuroendocrine signaling in Atlantic salmonDEVELOPMENTAL NEUROBIOLOGY, Issue 9 2010Anne-Grethe Gamst Moen Abstract Leptin and ghrelin are known to regulate energy homeostasis via hypothalamic neuropeptide signaling in mammals. Recent studies have discovered that these hormones exist in teleosts, however, very little is known concerning their role during teleost ontogeny. Here, we have examined the steady state levels of leptins, ghrelins, their target neuropetides and several growth factors during Atlantic salmon development. Initial experiments revealed differential expression of leptin genes and ghrelin isoforms during embryogenesis. In larvae, equal upregulation of ghrl1 and ghrl2 was observed just prior to exogenous feeding while a surge of lepa1 occurred one week after first-feeding. Subsequent dissection of the embryos and larvae showed that lepa1, cart, pomca1, and agrp are supplied as maternal transcripts. The earliest zygotic expression was observed for lepa1 and cart at 320 day degrees. By 400 day degrees, this expression was localized to the head and coincided with upregulation of ghrl2 and npy. Over the hatching period growth factor signaling predominated. The ghrelin surge prior to first-feeding was exclusively localized in the internal organs and coincided with upregulation of npy and agrp in the head and agrp in the trunk. One week after exogenous feeding was established major peaks were detected in the head for lepa1 and pomca1 with increasing levels of cart, while lepa1 was also significantly expressed in the trunk. By integrating theses data into an ontogenetic model, we suggest that the mediation of Atlantic salmon energy homeostatic pathways via endocrine and neuropeptide signaling retains putative features of the mammalian system. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 649,658, 2010 [source] Down-regulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signalingGENES TO CELLS, Issue 9 2008Hideko Hayashi The ERK MAP kinase and PI3-kinase/Akt pathways are major intracellular signaling modules, which are known to regulate diverse cellular processes including cell proliferation, survival and malignant transformation. However, it has not been fully understood how these two pathways interact with each other. Here, we demonstrate that inhibition of the ERK pathway by the MEK inhibitor U0126 or PD98059 significantly potentiates EGF- and FGF-induced Akt phosphorylation at both Thr308 and Ser473. We also show that hyperactivation of the ERK pathway greatly attenuates EGF- and FGF-induced Akt phosphorylation. Furthermore, the enhanced Akt phosphorylation induced by U0126 is inhibited by the PI3-kinase inhibitor LY294002, and is accompanied by the up-regulation of Ras activity. These results suggest that the ERK pathway inhibition enhances Akt phosphorylation through the Ras/PI3-kinase pathway. Thus, our results demonstrate that the ERK pathway negatively modulates the PI3-kinase/Akt pathway in response to growth factor stimulation. [source] Molecular mediators of metastasis in head and neck squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2005Gina M. S. Howell BA Abstract Background. The presence of regional metastasis in patients with head and neck squamous cell carcinoma (HNSCC) is a common and adverse event associated with poor prognosis and high mortality. Although significant improvements in standard therapies have increased the efficacy of local tumor management, the high incidence of tumor recurrence has resulted in limited improvements in overall survival rates. Understanding the molecular mechanisms that mediate HNSCC invasion and metastasis may enable identification of novel therapeutic targets for the prevention and management of tumor dissemination. Methods. A literature review was performed. Results. Several biologic mediators and mechanisms that have been implicated in HNSCC metastasis, such as cell adhesion molecules, proteolytic enzymes, growth factor signaling, metastasis suppressor genes, and chemokine receptors were reviewed. Conclusions. Prevention of HNSCC metastasis is an important clinical objective that requires an increased understanding of the molecular mechanisms of tumor invasion and dissemination. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Nonstructural 3/4A protease of hepatitis C virus activates epithelial growth factor,induced signal transduction by cleavage of the T-cell protein tyrosine phosphatase,HEPATOLOGY, Issue 6 2009Erwin Daniel Brenndörfer The hepatitis C virus (HCV) is a worldwide major cause of chronic liver disease with a high tendency to establish a persistent infection. To permit persistent replication of viral genomes through the cellular translation machinery without affecting host cell viability, viruses must have developed mechanisms to control cellular cascades required for sufficient viral replication, on the one hand, and to adapt viral replication to the cellular requirements on the other hand. The present study aimed to further elucidate mechanisms by which HCV targets growth factor signaling of the host cell and their implications for viral replication. The study describes a novel mechanism by which HCV influences the activation of the epithelial growth factor receptor/Akt pathway through a nonstructural (NS)3/4A-dependent down-regulation of the ubiquitously expressed tyrosine phosphatase T cell protein tyrosine phosphatase (TC-PTP). NS3/4A is demonstrated to cleave TC-PTP protease-dependently in vitro at two cleavage sites. The in vivo relevance of this finding is supported by the fact that down-regulation of TC-PTP protein expression could also be demonstrated in HCV-infected individuals and in transgenic mice with intrahepatic expression of NS3/4A. Conclusion: This down-regulation of TC-PTP results in an enhancement of epithelial growth factor (EGF)-induced signal transduction and increases basal activity of Akt, which is demonstrated to be essential for the maintenance of sufficient viral replication. Hence, therapeutic targeting of NS3/4A may not only disturb viral replication by blocking the processing of the viral polyprotein but also exerts unforeseen indirect antiviral effects, further diminishing viral replication. (HEPATOLOGY 2009;49:1810,1820.) [source] Ethanol-Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Placenta: Relevance to Pregnancy LossALCOHOLISM, Issue 3 2010Fusun Gundogan Background:, Ethanol consumption during pregnancy increases the risk of early pregnancy loss and causes intrauterine growth restriction. We previously showed that chronic gestational exposure to ethanol impairs placentation, and that this effect is associated with inhibition of insulin and insulin growth factor signaling. Since ethanol also causes oxidative stress and DNA damage, we extended our investigations to assess the role of these pathological processes on placentation and placental gene expression. Methods:, Pregnant Long Evans rats were pair-fed liquid diets containing 0% or 24% ethanol by caloric content. Placentas harvested on gestation day 16 were used to examine DNA damage, lipid peroxidation, apoptosis, mitochondrial gene/protein and hormonal gene expression in relation to ethanol exposure. Results:, Gestational exposure to ethanol increased fetal resorption, and trophoblast apoptosis/necrosis, oxidative stress, DNA damage, and lipid peroxidation. These adverse effects of ethanol were associated with increased expression of pro-apoptotic (Bax and Bak) and reduced levels of the anti-apoptotic Bcl-2 protein. In addition, increased trophoblast apoptosis proneness was associated with p53-independent activation of p21, reduced mitochondrial gene and protein expression, and dysregulated expression of prolactin (PRL) family hormones that are required for implantation and pregnancy-related adaptations. Conclusions:, Chronic gestational exposure to ethanol increases fetal demise due to impaired survival and mitochondrial function, increased oxidative stress, DNA damage and lipid peroxidation, and dysregulated expression of prolactin family hormones in placental trophoblasts. [source] | |||||||||||||