scholarly journals Involvement of the VEGF signaling pathway in immunosuppression and hypoxia stress: analysis of mRNA expression in lymphocytes mediating panting in Jersey cattle under heat stress

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jian Wang ◽  
Yang Xiang ◽  
Shisong Jiang ◽  
Hongchang Li ◽  
Flurin Caviezel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Stress ◽  
Gas Exchange ◽  
Dairy Cattle ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Oxygen Regulation ◽  
Vegf Signaling ◽  
Jersey Cattle ◽  
Vegf Signaling Pathway

Abstract Background Extreme panting under heat stress threatens dairy cattle milk production. Previous research has revealed that the gas exchange-mediated respiratory drive in critically ill dairy cattle with low O2 saturation induces panting. Vascular endothelial growth factor (VEGF) signaling may play important roles in immunosuppression and oxidative stress during severe respiratory stress responses in heat-stressed cattle. The objectives of this study were to transcriptomically analyze mRNA expression mediating heat-induced respiratory stress-associated panting, evaluate gas exchange, screen hub genes, and verify the expression of proteins encoded by differentially expressed genes in lymphocyte pathways. Results Jersey cattle were naturally heat-exposed. Physiological data were collected for response evaluation, and blood was collected for gas exchange and gene expression assays at 06:00, 10:00 and 14:00 continuously for 1 week. Lymphocytes were isolated from whole-blood samples for mRNA-seq and expression analysis of key pathway genes/proteins. The cattle respiration rates differed with time, averaging 51 bpm at 06:00, 76 bpm at 10:00, and 121 bpm at 14:00 (p < 0.05). Gas exchange analysis showed that both pH and pCO2 differed with time: they were 7.41 and 41 mmHg at 06:00, 7.45 and 37.5 mmHg at 10:00, and 7.49 and 33 mmHg at 14:00, respectively (p < 0.01). Sixteen heat-related differentially expressed genes (DEGs; 13 upregulated and 3 downregulated) were screened between 212 DEGs and 1370 heat stress-affected genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) hub gene functional analysis annotated eleven genes to signal transduction, six genes to the immune response, and five genes to the endocrine response, including both prostaglandin-endoperoxide synthase 2 (PTGS2) and VEGF. Gene Ontology (GO) functional enrichment analysis revealed that oxygen regulation was associated with the phosphorus metabolic process, response to oxygen levels, response to decreased oxygen levels, response to hypoxia and cytokine activity terms. The main signaling pathways were the VEGF, hypoxia inducible factor-1(HIF-1), cytokine-cytokine receptor interaction and TNF pathways. Four genes involved Integrin beta 3 (ITBG3), PTGS2, VEGF, and myosin light chain 9 (MYL9) among the 16 genes related to immunosuppression, oxidative stress, and endocrine dysfunction were identified as participants in the VEGF signaling pathway and oxygenation. Conclusion These findings help elucidate the underlying immune and oxygen regulation mechanisms associated with the VEGF signaling pathway in heat-stressed dairy cattle.

scholarly journals Involvement of the VEGF Signaling Pathway in Immunosuppression and Hypoxia Stress: Analysis of mRNA Expression in Lymphocytes Mediating Panting in Jersey Cattle under Heat Stress

2021 ◽  
Author(s):  
jian wang ◽  
Yang Xiang ◽  
Shisong Jiang ◽  
Hongchang Li ◽  
Caviezel Flurin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Stress ◽  
Gas Exchange ◽  
Dairy Cattle ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Oxygen Regulation ◽  
Vegf Signaling ◽  
Jersey Cattle ◽  
Vegf Signaling Pathway

Abstract Background: Extreme panting under heat stress threatens dairy cattle milk production. Previous research has revealed that the gas exchange-mediated respiratory drive in critically ill dairy cattle with low O2 saturation induces panting. Vascular endothelial growth factor (VEGF) signaling may play important roles in immunosuppression and oxidative stress during severe respiratory stress responses in heat-stressed cattle. The objectives of this study were to transcriptomically analyze mRNA expression mediating heat-induced respiratory stress-associated panting, evaluate gas exchange, screen hub genes, and verify the expression of proteins encoded by differentially expressed genes in lymphocyte pathways. Results: Jersey cattle were naturally heat-exposed. Physiological data were collected for response evaluation, and blood was collected for gas exchange and gene expression assays at 06:00, 10:00 and 14:00 continuously for one week. Lymphocytes were isolated from whole-blood samples for mRNA-seq and expression analysis of key pathway genes/proteins. The cattle respiration rates differed with time, averaging 51 bpm at 06:00, 76 bpm at 10:00, and 121 bpm at 14:00 (p < 0.05). Gas exchange analysis showed that both pH and pCO2 differed with time: they were 7.41 and 41 mmHg at 06:00, 7.45 and 37.5 mmHg at 10:00, and 7.49 and 33 mmHg at 14:00, respectively (p < 0.01). Sixteen heat-related differentially expressed genes (DEGs; 13 upregulated and 3 downregulated) were screened between 212 DEGs and 1370 heat stress-affected genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) hub gene functional analysis annotated eleven genes to signal transduction, six genes to the immune response, and five genes to the endocrine response, including both prostaglandin-endoperoxide synthase 2 (PTGS2) and VEGF. Gene Ontology(GO) functional enrichment analysis revealed that oxygen regulation was associated with the phosphorus metabolic process, response to oxygen levels, response to decreased oxygen levels, response to hypoxia and cytokine activity terms. The main signaling pathways were the VEGF, hypoxia inducible factor-1(HIF-1), cytokine-cytokine receptor interaction and TNF pathways. Four genes involved Integrin beta 3 (ITBG3), PTGS2, VEGF, and myosin light chain 9 (MYL9) among the 16 genes related to immunosuppression, oxidative stress, and endocrine dysfunction were identified as participants in the VEGF signaling pathway and oxygenation. Conclusion: These findings help elucidate the underlying immune and oxygen regulation mechanisms associated with the VEGF signaling pathway in heat-stressed dairy cattle.

PTEN regulate angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells

2009 ◽  
Vol 331 (1-2) ◽  
pp. 161-171 ◽  
Author(s):  
Jiachi Ma ◽  
Hirozumi Sawai ◽  
Nobuo Ochi ◽  
Yoichi Matsuo ◽  
Donghui Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Pancreatic Cancer ◽  
Vegf Signaling ◽  
Pancreatic Cancer Cells ◽  
Vegf Signaling Pathway

scholarly journals Potential Role of A2BAdenosine Receptors on Proliferation/Migration of Fetal Endothelium Derived from Preeclamptic Pregnancies

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jesenia Acurio ◽  
Felipe Troncoso ◽  
Patricio Bertoglia ◽  
Carlos Salomon ◽  
Claudio Aguayo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Adenosine Receptor ◽  
Protein Level ◽  
Normal Pregnancy ◽  
Endothelial Cell Proliferation ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway ◽  
In Cells

To investigate the functionality ofA2Badenosine receptor (A2BAR) and the nitric oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the endothelial cell proliferation/migration during preeclampsia, we used human umbilical vein endothelial cells (HUVECs) isolated from normal pregnanciesn=15or pregnancies with preeclampsian=15. Experiments were performed in presence or absence of the nonselective adenosine receptor agonist NECA, theA2BAR selective antagonist MRS-1754, and the nitric oxide synthase (NOS) inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a significant higher protein level ofA2BAR and logEC50for NECA-mediated proliferation than normotensive pregnancies. The stimulatory effect of NECA (10 μM, 24 h) on cell proliferation was prevented by MRS-1754 (5 nM) coincubation only in cells from normotensive pregnancies. Nevertheless, L-NAME (100 μM, 24 h) reduced the NECA-induced cell proliferation/migration in HUVEC from normal pregnancy; however in preeclampsia only NECA-induced cell proliferation was reduced by L-NAME. Moreover, NECA increased protein nitration and abundance of VEGF in cells from normal pregnancy and effect prevented by MRS-1754 coincubation. Nevertheless, in preeclampsia NECA did not affect the protein level of VEGF. In conclusion HUVECs from preeclampsia exhibit elevated protein level ofA2BAR and impairment ofA2BAR-mediated NO/VEGF signaling pathway.

scholarly journals Targeting the IKKβ/mTOR/VEGF Signaling Pathway as a Potential Therapeutic Strategy for Obesity-Related Breast Cancer

2012 ◽  
Vol 11 (10) ◽  
pp. 2212-2221 ◽  
Author(s):  
Chun-Te Chen ◽  
Yi Du ◽  
Hirohito Yamaguchi ◽  
Jung-Mao Hsu ◽  
Hsu-Ping Kuo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Therapeutic Strategy ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway

Blood pressure (BP) as a biomarker for sorafenib (S), an inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2035-2035 ◽  
Author(s):  
M. L. Maitland ◽  
K. Moshier ◽  
J. Imperial ◽  
K. E. Kasza ◽  
T. Karrison ◽  
...  
Keyword(s):  
Steady State ◽  
Signaling Pathway ◽  
Performance Status ◽  
Plasma Concentrations ◽  
Cancer Therapeutics ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway ◽  
State Plasma

2035 Background: Hypertension is a commonly reported toxicity of agents that inhibit the VEGF signaling pathway (VSP). This new class of cancer therapeutics has broad activity, but optimal dosing methods and integration into established treatment regimens could be enhanced by identification of reliable biomarkers. S, a new treatment for advanced renal cell carcinoma, is an orally available inhibitor of multiple VSP kinases including Raf-1 and VEGFR2. To characterize the chronicity and interindividual variability of BP responses to VSP inhibition we collected serial, standardized measures of BP and concurrent steady-state plasma concentrations ([plasma]) of S, from 30 patients (pts). Methods: Pts with advanced solid tumors, ECOG performance status < 2, and screening BP ≤ 140/90 mmHg on no more than one antihypertensive agent took 400mg S twice daily. Prior to therapy and at 3 time points after steady state [plasma] of drug was achieved, pts underwent 24-hour ambulatory BP monitoring with the SunTech Oscar PowerPack 2 (SunTech Medical, Morrisville, North Carolina). Readings were collected every 15 minutes during daytime hours and every 45 minutes overnight. Results: Unweigthed mean and standard deviations (sd) of systolic (SBP) and diastolic (DBP) 24-hr BP measurements were calculated for each pt. for the sessions pre-therapy and when steady state [plasma] S was reached (between days 6–10 after starting treatment). The differences in mean BPs between the two sessions were compared with (and p values reported for) paired t-tests. Regression analysis of [plasma] of S with either DBP or SBP, or change in DBP or SBP, with main effect and interaction terms for albumin, age, and sex revealed no significant correlation between S [plasma] and BP response. Conclusions: BP elevation is a biomarker for VSP inhibition. The known variability (coefficient of variation = 70%) in total S steady state plasma concentrations did not account for the observed variability in BP response. [Table: see text] [Table: see text]

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