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Qin Yan - One of the best experts on this subject based on the ideXlab platform.

  • GNA11 differentially mediates fibroblast growth factor 2 and vascular endothelial growth factor a induced cellular responses in human fetoplacental endothelial cells
    The Journal of Physiology, 2018
    Co-Authors: Qing-yun Zou, Ying-jie Zhao, Xiangzhen Wang, Aixia Liu, Xinqi Zhong, Qin Yan
    Abstract:

    KEY POINTS Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P < 0.05) FGF2- and VEGFA-stimulated fetoplacental endothelial migration (by ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P < 0.05) FGF2- and VEGFA-induced phosphorylation of phospholipase C-β3 (PLCβ3) at S537 in a time-dependent fashion but not mitogen-activated protein kinase 3/1 (ERK1/2) and v-akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2- and VEGFA-stimulated fetoplacental endothelial cell migration partially via altering the activation of PLCβ3.

  • GNA11 differentially mediates fibroblast growth factor 2- and vascular endothelial growth factor A-induced cellular responses in human fetoplacental endothelial cells.
    The Journal of physiology, 2018
    Co-Authors: Qing-yun Zou, Ying-jie Zhao, Qin Yan, Xiang‐zhen Wang, Ai‐xia Liu, Xin‐qi Zhong, Chi Zhou, Jing Zheng
    Abstract:

    KEY POINTS Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P 

Ricardo Santiago Gomez - One of the best experts on this subject based on the ideXlab platform.

  • Oral pyogenic granulomas show MAPK/ERK signaling pathway activation, which occurs independently of BRAF, KRAS, HRAS, NRAS, GNA11, and GNA14 mutations.
    Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pat, 2019
    Co-Authors: Thaís Dos Santos Fontes Pereira, Larissa Stefhanne Damasceno De Amorim, Núbia Braga Pereira, Jéssica Gardone Vitório, Filipe Fideles Duarte-andrade, Letícia Martins Guimarães, Marina Gonçalves Diniz, Carolina Cavaliéri Gomes, Ricardo Santiago Gomez
    Abstract:

    Background Pyogenic granuloma (PG) is a benign nodular lesion with a prominent vascular component which may affect different sites. Recently, BRAF, KRAS, HRAS, NRAS, GNA11, and GNA14 mutations were reported on PGs of the skin. The present study assessed the role of the MAPK/ERK pathway in oral PG pathogenesis. Methods Mutations in hotspot regions of genes involved in the MAPK/ERK pathway activation were investigated by Sanger sequencing. The expression of phospho-ERK1/2 was evaluated by immunohistochemistry. Results Oral PGs did not show mutations in the sequenced regions of the genes BRAF, KRAS, HRAS, NRAS, GNA11, or GNA14. Our results also showed activation of the MAPK/ERK pathway demonstrated by phospho-ERK1/2 immunohistochemical positivity. Conclusions Although oral PG shows MAPK/ERK pathway activation, the driver molecular event remains to be elucidated.

  • oral pyogenic granulomas show mapk erk signaling pathway activation which occurs independently of braf kras hras nras GNA11 and gna14 mutations
    Journal of Oral Pathology & Medicine, 2019
    Co-Authors: Thaís Dos Santos Fontes Pereira, Larissa Stefhanne Damasceno De Amorim, Núbia Braga Pereira, Jéssica Gardone Vitório, Letícia Martins Guimarães, Marina Gonçalves Diniz, Carolina Cavaliéri Gomes, Filipe Fideles Duarteandrade, Ricardo Santiago Gomez
    Abstract:

    Background Pyogenic granuloma (PG) is a benign nodular lesion with a prominent vascular component which may affect different sites. Recently, BRAF, KRAS, HRAS, NRAS, GNA11, and GNA14 mutations were reported on PGs of the skin. The present study assessed the role of the MAPK/ERK pathway in oral PG pathogenesis. Methods Mutations in hotspot regions of genes involved in the MAPK/ERK pathway activation were investigated by Sanger sequencing. The expression of phospho-ERK1/2 was evaluated by immunohistochemistry. Results Oral PGs did not show mutations in the sequenced regions of the genes BRAF, KRAS, HRAS, NRAS, GNA11, or GNA14. Our results also showed activation of the MAPK/ERK pathway demonstrated by phospho-ERK1/2 immunohistochemical positivity. Conclusions Although oral PG shows MAPK/ERK pathway activation, the driver molecular event remains to be elucidated.

  • Molecular and immunohistochemical analyses of uveal melanoma patient cohort.
    Melanoma research, 2019
    Co-Authors: Helena C. Sarubi, Núbia Braga Pereira, Carolina Cavaliéri Gomes, Ricardo Santiago Gomez, Ana Carolina De Melo Do Carmo, Flavia M. Melo, Luciana Bastos-rodrigues, Moisés Salgado Pedrosa, Eitan Friedman, Luiz De Marco
    Abstract:

    Uveal melanoma is a rare form of melanoma and the most frequent primary eye malignancy in adults. The major molecular alterations underlying uveal melanoma pathogenesis affect mainly the GNAQ, GNA11, SF3B1, and BAP1 genes. In this study, we somatically genotyped 31 Brazilian uveal melanomas for BRAF, GNA11, GNAQ, SF3B1, and BAP1 gene mutations and assessed BRCA2 and p53 protein expression. GNAQ and GNA11 mutations were detected in 60%, and SF3B1 mutation rate was 30%. p53 Immunostaining was markedly positive in 5/31, and 3/31 samples showed negative BRCA2 expression. This study supports the importance of these key genes in uveal melanoma tumorigenesis; p53 and BRCA pathways seem to play a role in a subset of patients, possibly heralding unfavorable prognosis.

Tilmann Volk - One of the best experts on this subject based on the ideXlab platform.

  • Larger transient outward K^+ current and shorter action potential duration in Gα_11 mutant mice
    Pflügers Archiv - European Journal of Physiology, 2010
    Co-Authors: Michael Wagner, Elena Rudakova, Vera Schütz, Magdalena Frank, Heimo Ehmke, Tilmann Volk
    Abstract:

    The α_1-adrenoceptor as well as the AT_1- and the ET_A-receptor couple to G-proteins of the Gα_q/11 family and contribute to the regulation of the transient outward K^+ current (I_to,f) under pathological conditions such as cardiac hypertrophy or failure. This suggests an important role of Gα_q/11-signalling in the physiological regulation of I_to,f. Here, we investigate mice deficient of the Gα_11 protein (GNA11^−/−) to clarify the physiological role of Gα_11 signalling in cardiac ion channel regulation. Myocytes from endocardial and epicardial layers were isolated from the left ventricular free wall and investigated using the ruptured-patch whole-cell patch-clamp technique. At +40 mV, epicardial myocytes from GNA11^−/− mice displayed a 23% larger I_to,f than controls (52.6 ± 4.1 pApF^−1, n  = 20 vs 42.7 ± 2.8 pApF^−1, n  = 26, p  

  • Larger transient outward K+ current and shorter action potential duration in Gα11 mutant mice
    Pflugers Archiv : European journal of physiology, 2009
    Co-Authors: Michael Wagner, Elena Rudakova, Vera Schütz, Magdalena Frank, Heimo Ehmke, Tilmann Volk
    Abstract:

    The α1-adrenoceptor as well as the AT1- and the ETA-receptor couple to G-proteins of the Gαq/11 family and contribute to the regulation of the transient outward K+ current (Ito,f) under pathological conditions such as cardiac hypertrophy or failure. This suggests an important role of Gαq/11-signalling in the physiological regulation of Ito,f. Here, we investigate mice deficient of the Gα11 protein (GNA11−/−) to clarify the physiological role of Gα11 signalling in cardiac ion channel regulation. Myocytes from endocardial and epicardial layers were isolated from the left ventricular free wall and investigated using the ruptured-patch whole-cell patch-clamp technique. At +40 mV, epicardial myocytes from GNA11−/− mice displayed a 23% larger Ito,f than controls (52.6 ± 4.1 pApF−1, n = 20 vs 42.7 ± 2.8 pApF−1, n = 26, p < 0.05). Endocardial Ito,f was similar in GNA11−/− mice and controls. With the except of minor changes in endocardial myocytes, Ito,f kinetics were similar in both groups. In the epicardial layer, western blot analysis revealed a 19% higher expression of the K+-channel α-subunit Kv4.2 in GNA11−/− mice than in wild type (wt; p < 0.05). The β-subunit KChIP2b was upregulated by 102% in epicardial myocytes of GNA11−/− mice (p < 0.01, n = 4). Consistent with the difference in Ito,f, action potential duration was shorter in epicardial cells of GNA11−/− mice than in wt (p < 0.05), while no difference was found in endocardial myocytes. These results suggest that Gα11-coupled signalling is a central pathway in the regulation of Ito,f. It physiologically exerts a tonic inhibitory influence on the expression of Ito,f and thereby contributes to the regulation of cardiac repolarisation.

Ying-jie Zhao - One of the best experts on this subject based on the ideXlab platform.

  • GNA11 differentially mediates fibroblast growth factor 2 and vascular endothelial growth factor a induced cellular responses in human fetoplacental endothelial cells
    The Journal of Physiology, 2018
    Co-Authors: Qing-yun Zou, Ying-jie Zhao, Xiangzhen Wang, Aixia Liu, Xinqi Zhong, Qin Yan
    Abstract:

    KEY POINTS Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P < 0.05) FGF2- and VEGFA-stimulated fetoplacental endothelial migration (by ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P < 0.05) FGF2- and VEGFA-induced phosphorylation of phospholipase C-β3 (PLCβ3) at S537 in a time-dependent fashion but not mitogen-activated protein kinase 3/1 (ERK1/2) and v-akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2- and VEGFA-stimulated fetoplacental endothelial cell migration partially via altering the activation of PLCβ3.

  • GNA11 differentially mediates fibroblast growth factor 2- and vascular endothelial growth factor A-induced cellular responses in human fetoplacental endothelial cells.
    The Journal of physiology, 2018
    Co-Authors: Qing-yun Zou, Ying-jie Zhao, Qin Yan, Xiang‐zhen Wang, Ai‐xia Liu, Xin‐qi Zhong, Chi Zhou, Jing Zheng
    Abstract:

    KEY POINTS Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P 

  • Expression of G-Protein Subunit α-14 Is Increased in Human Placentas from Preeclamptic Pregnancies
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2014
    Co-Authors: Ying-jie Zhao, Qing-yun Zou, Kai Wang, Jing Zheng
    Abstract:

    G-proteins mediate cellular function upon interaction with G-protein coupled receptors. Of the 16 mammalian G-protein α subunits identified, G-protein subunit α-11 (GNA11) and -14 (GNA14) have been implicated in modulating hypertension and endothelial function. However, little is known about their expression and roles in human placentas. Here, we examined GNA11 and GNA14 protein expression in first trimester (FT), normal term (NT), and severe preeclamptic (sPE) human placentas as well as in NT human umbilical cords. We found that GNA11 and GNA14 were immunolocalized primarily in trophoblasts, villous stromal cells, and endothelial cells in placentas as well as in endothelial and/or smooth muscle cells of the umbilical cord artery and vein. Western blotting revealed that the GNA14, but not GNA11, protein levels were increased (2.5-2.9 fold; p

Qing-yun Zou - One of the best experts on this subject based on the ideXlab platform.

  • GNA11 differentially mediates fibroblast growth factor 2 and vascular endothelial growth factor a induced cellular responses in human fetoplacental endothelial cells
    The Journal of Physiology, 2018
    Co-Authors: Qing-yun Zou, Ying-jie Zhao, Xiangzhen Wang, Aixia Liu, Xinqi Zhong, Qin Yan
    Abstract:

    KEY POINTS Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P < 0.05) FGF2- and VEGFA-stimulated fetoplacental endothelial migration (by ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P < 0.05) FGF2- and VEGFA-induced phosphorylation of phospholipase C-β3 (PLCβ3) at S537 in a time-dependent fashion but not mitogen-activated protein kinase 3/1 (ERK1/2) and v-akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2- and VEGFA-stimulated fetoplacental endothelial cell migration partially via altering the activation of PLCβ3.

  • GNA11 differentially mediates fibroblast growth factor 2- and vascular endothelial growth factor A-induced cellular responses in human fetoplacental endothelial cells.
    The Journal of physiology, 2018
    Co-Authors: Qing-yun Zou, Ying-jie Zhao, Qin Yan, Xiang‐zhen Wang, Ai‐xia Liu, Xin‐qi Zhong, Chi Zhou, Jing Zheng
    Abstract:

    KEY POINTS Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2- and VEGFA-induced endothelial cell responses under physiological chronic low O2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2- and VEGFA-induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C-β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2- and VEGFA-induced fetoplacental endothelial function. ABSTRACT During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein α subunits q (GNAq) and 11 (GNA11) are two members of the Gαq/11 subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O2 (3% O2 ), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P 

  • Expression of G-Protein Subunit α-14 Is Increased in Human Placentas from Preeclamptic Pregnancies
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2014
    Co-Authors: Ying-jie Zhao, Qing-yun Zou, Kai Wang, Jing Zheng
    Abstract:

    G-proteins mediate cellular function upon interaction with G-protein coupled receptors. Of the 16 mammalian G-protein α subunits identified, G-protein subunit α-11 (GNA11) and -14 (GNA14) have been implicated in modulating hypertension and endothelial function. However, little is known about their expression and roles in human placentas. Here, we examined GNA11 and GNA14 protein expression in first trimester (FT), normal term (NT), and severe preeclamptic (sPE) human placentas as well as in NT human umbilical cords. We found that GNA11 and GNA14 were immunolocalized primarily in trophoblasts, villous stromal cells, and endothelial cells in placentas as well as in endothelial and/or smooth muscle cells of the umbilical cord artery and vein. Western blotting revealed that the GNA14, but not GNA11, protein levels were increased (2.5-2.9 fold; p