LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 22

Search options

  1. Article ; Online: The quiescent endothelium: signalling pathways regulating organ-specific endothelial normalcy.

    Ricard, Nicolas / Bailly, Sabine / Guignabert, Christophe / Simons, Michael

    Nature reviews. Cardiology

    2021  Volume 18, Issue 8, Page(s) 565–580

    Abstract: Endothelial cells are at the interface between circulating blood and tissues. This position confers on them a crucial role in controlling oxygen and nutrient exchange and cellular trafficking between blood and the perfused organs. The endothelium adopts ... ...

    Abstract Endothelial cells are at the interface between circulating blood and tissues. This position confers on them a crucial role in controlling oxygen and nutrient exchange and cellular trafficking between blood and the perfused organs. The endothelium adopts a structure that is specific to the needs and function of each tissue and organ and is subject to tissue-specific signalling input. In adults, endothelial cells are quiescent, meaning that they are not proliferating. Quiescence was considered to be a state in which endothelial cells are not stimulated but are instead slumbering and awaiting activating signals. However, new evidence shows that quiescent endothelium is fully awake, that it constantly receives and initiates functionally important signalling inputs and that this state is actively regulated. Signalling pathways involved in the maintenance of functionally quiescent endothelia are starting to be identified and are a combination of endocrine, autocrine, paracrine and mechanical inputs. The paracrine pathways confer a microenvironment on the endothelial cells that is specific to the perfused organs and tissues. In this Review, we present the current knowledge of organ-specific signalling pathways involved in the maintenance of endothelial quiescence and the pathologies associated with their disruption. Linking organ-specific pathways and human vascular pathologies will pave the way towards the development of innovative preventive strategies and the identification of new therapeutic targets.
    MeSH term(s) Endothelium/physiology ; Humans ; Signal Transduction
    Language English
    Publishing date 2021-02-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2490375-9
    ISSN 1759-5010 ; 1759-5002
    ISSN (online) 1759-5010
    ISSN 1759-5002
    DOI 10.1038/s41569-021-00517-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6019: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 98: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: When it is better to regress: dynamics of vascular pruning.

    Ricard, Nicolas / Simons, Michael

    PLoS biology

    2015  Volume 13, Issue 5, Page(s) e1002148

    Abstract: Blood vascular networks in vertebrates are essential to tissue survival. Establishment of a fully functional vasculature is complex and requires a number of steps including vasculogenesis and angiogenesis that are followed by differentiation into ... ...

    Abstract Blood vascular networks in vertebrates are essential to tissue survival. Establishment of a fully functional vasculature is complex and requires a number of steps including vasculogenesis and angiogenesis that are followed by differentiation into specialized vascular tissues (i.e., arteries, veins, and lymphatics) and organ-specific differentiation. However, an equally essential step in this process is the pruning of excessive blood vessels. Recent studies have shown that pruning is critical for the effective perfusion of blood into tissues. Despite its significance, vessel pruning is the least understood process in vascular differentiation and development. Two recently published PLOS Biology papers provide important new information about cellular dynamics of vascular regression.
    MeSH term(s) Animals ; Blood Vessels/growth & development ; Vascular Remodeling
    Language English
    Publishing date 2015-05-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.1002148
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6193: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Isoform-Specific Roles of ERK1 and ERK2 in Arteriogenesis.

    Ricard, Nicolas / Zhang, Jiasheng / Zhuang, Zhen W / Simons, Michael

    Cells

    2019  Volume 9, Issue 1

    Abstract: Despite the clinical importance of arteriogenesis, this biological process is poorly understood. ERK1 and ERK2 are key components of a major intracellular signaling pathway activated by vascular endothelial growth (VEGF) and FGF2, growth factors critical ...

    Abstract Despite the clinical importance of arteriogenesis, this biological process is poorly understood. ERK1 and ERK2 are key components of a major intracellular signaling pathway activated by vascular endothelial growth (VEGF) and FGF2, growth factors critical to arteriogenesis. To investigate the specific role of each ERK isoform in arteriogenesis, we used mice with a global
    MeSH term(s) Animals ; Arteries/enzymology ; Arteries/growth & development ; Cell Proliferation/physiology ; Cells, Cultured ; Female ; Human Umbilical Vein Endothelial Cells ; Humans ; Isoenzymes/metabolism ; MAP Kinase Signaling System ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Myocytes, Smooth Muscle/metabolism ; Neovascularization, Physiologic ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Isoenzymes ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse ; MAPK1 protein, human (EC 2.7.11.24) ; MAPK3 protein, human (EC 2.7.11.24) ; Mapk1 protein, mouse (EC 2.7.11.24) ; Mapk3 protein, mouse (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24)
    Language English
    Publishing date 2019-12-21
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9010038
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Fox(y) regulators of VEGF receptors.

    Ricard, Nicolas / Simons, Michael

    Circulation research

    2014  Volume 115, Issue 8, Page(s) 683–685

    MeSH term(s) Animals ; Blood Vessels/metabolism ; Endothelial Cells/metabolism ; Forkhead Transcription Factors/metabolism ; Humans ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Forkhead Transcription Factors ; Foxf1 protein, mouse ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2014-09-25
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.114.304974
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ui IV Zs.70: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Ui IV Zs.60: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Disrupted BMP-9 Signaling Impairs Pulmonary Vascular Integrity in Hepatopulmonary Syndrome.

    Robert, Fabien / Certain, Marie-Caroline / Baron, Audrey / Thuillet, Raphaël / Duhaut, Léa / Ottaviani, Mina / Kamel Chelgham, Mustapha / Normand, Corinne / Berrebeh, Nihel / Ricard, Nicolas / Furlan, Valerie / Desroches-Castan, Agnès / Gonzales, Emmanuel / Jacquemin, Emmanuel / Sitbon, Olivier / Humbert, Marc / Bailly, Sabine / Coilly, Audrey / Guignabert, Christophe /
    Tu, Ly / Savale, Laurent

    American journal of respiratory and critical care medicine

    2024  

    Abstract: Rationale: Hepatopulmonary syndrome (HPS) is a severe complication of liver diseases characterized by abnormal dilatation of pulmonary vessels, resulting in impaired oxygenation. Recent research highlights the pivotal role of liver-produced bone ... ...

    Abstract Rationale: Hepatopulmonary syndrome (HPS) is a severe complication of liver diseases characterized by abnormal dilatation of pulmonary vessels, resulting in impaired oxygenation. Recent research highlights the pivotal role of liver-produced bone morphogenetic protein (BMP)-9 in maintaining pulmonary vascular integrity.
    Objectives: This study aimed to investigate the involvement of BMP-9 in human and experimental HPS.
    Methods: Circulating BMP-9 levels were measured in 63 healthy controls and 203 cirrhotic patients, with or without HPS. Two animal models of portal hypertension were employed: common bile duct ligation (CBDL) with cirrhosis and long-term partial portal vein ligation (PPVL) without cirrhosis. Additionally, the therapeutic effect of low-dose BMP activator FK506 was investigated, and the pulmonary vascular phenotype of BMP-9 knockout rats was analyzed.
    Measurements and main results: Patients with HPS related to compensated cirrhosis demonstrated lower levels of circulating BMP-9 compared to patients without HPS. Severe cirrhosis patients exhibited consistently low levels of BMP-9. In animal models, HPS characteristics, including intrapulmonary vascular dilations (IPVDs) and alveolo-arterial gradient enlargement, were observed. HPS development in both rat models correlated with reduced intrahepatic BMP-9 expression, decreased circulating BMP-9 level and activity, and impaired pulmonary BMP-9 endothelial pathway. Daily treatment with FK506 for 2-weeks restored BMP pathway in the lungs, alleviating IPVDs, and improving gas exchange impairment. Furthermore, BMP-9 knockout rats displayed a pulmonary HPS phenotype, supporting its role in disease progression.
    Conclusion: The study findings suggest that portal hypertension-induced loss of BMP-9 signaling contributes to HPS development.
    Language English
    Publishing date 2024-04-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202307-1289OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uh II Zs.80: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Differential Consequences of

    Desroches-Castan, Agnès / Tillet, Emmanuelle / Ricard, Nicolas / Ouarné, Marie / Mallet, Christine / Feige, Jean-Jacques / Bailly, Sabine

    Cells

    2019  Volume 8, Issue 9

    Abstract: The aim of the present work was to address the role of BMP9 in different genetic backgrounds (C57BL/6, BALB/c, and 129/Ola) of mice deleted ... ...

    Abstract The aim of the present work was to address the role of BMP9 in different genetic backgrounds (C57BL/6, BALB/c, and 129/Ola) of mice deleted for
    MeSH term(s) Animals ; Biomarkers/metabolism ; Capillaries/metabolism ; Capillaries/pathology ; Cell Differentiation ; Disease Models, Animal ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Growth Differentiation Factor 2/genetics ; Growth Differentiation Factor 2/physiology ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/genetics ; Liver Cirrhosis/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL
    Chemical Substances Biomarkers ; Gdf2 protein, mouse ; Growth Differentiation Factor 2
    Language English
    Publishing date 2019-09-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells8091079
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.

    Zarkada, Georgia / Chen, Xun / Zhou, Xuetong / Lange, Martin / Zeng, Lei / Lv, Wenyu / Zhang, Xuan / Li, Yunhua / Zhou, Weibin / Liu, Keli / Chen, Dongying / Ricard, Nicolas / Liao, James / Kim, Young-Bum / Benedito, Rui / Claesson-Welsh, Lena / Alitalo, Kari / Simons, Michael / Ju, Rong /
    Li, Xuri / Eichmann, Anne / Zhang, Feng

    Circulation research

    2023  Volume 133, Issue 4, Page(s) 333–349

    Abstract: Background: Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas ... ...

    Abstract Background: Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood.
    Methods: We used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries.
    Results: By studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction.
    Conclusions: Our results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.
    MeSH term(s) Mice ; Animals ; Vascular Endothelial Growth Factor A/metabolism ; Endothelial Cells/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Chylomicrons/metabolism ; Lymphatic Vessels/metabolism ; Monomeric GTP-Binding Proteins/metabolism ; Capillary Permeability
    Chemical Substances Vascular Endothelial Growth Factor A ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Chylomicrons ; Monomeric GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2023-07-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.123.322607
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ui IV Zs.70: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Ui IV Zs.60: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: New molecular targets of pulmonary vascular remodeling in pulmonary arterial hypertension: importance of endothelial communication.

    Guignabert, Christophe / Tu, Ly / Girerd, Barbara / Ricard, Nicolas / Huertas, Alice / Montani, David / Humbert, Marc

    Chest

    2015  Volume 147, Issue 2, Page(s) 529–537

    Abstract: Pulmonary arterial hypertension (PAH) is a disorder in which mechanical obstruction of the pulmonary vascular bed is largely responsible for the rise in mean pulmonary arterial pressure, resulting in a progressive functional decline despite current ... ...

    Abstract Pulmonary arterial hypertension (PAH) is a disorder in which mechanical obstruction of the pulmonary vascular bed is largely responsible for the rise in mean pulmonary arterial pressure, resulting in a progressive functional decline despite current available therapeutic options. The fundamental pathogenetic mechanisms underlying this disorder include pulmonary vasoconstriction, in situ thrombosis, medial hypertrophy, and intimal proliferation, leading to occlusion of the small to mid-sized pulmonary arterioles and the formation of plexiform lesions. Several predisposing or promoting mechanisms that contribute to excessive pulmonary vascular remodeling in PAH have emerged, such as altered crosstalk between cells within the vascular wall, sustained inflammation and dysimmunity, inhibition of cell death, and excessive activation of signaling pathways, in addition to the impact of systemic hormones, local growth factors, cytokines, transcription factors, and germline mutations. Although the spectrum of therapeutic options for PAH has expanded in the last 20 years, available therapies remain essentially palliative. However, over the past decade, a better understanding of new key regulators of this irreversible pulmonary vascular remodeling has been obtained. This review examines the state-of-the-art potential new targets for innovative research in PAH, focusing on (1) the crosstalk between cells within the pulmonary vascular wall, with particular attention to the role played by dysfunctional endothelial cells; (2) aberrant inflammatory and immune responses; (3) the abnormal extracellular matrix function; and (4) altered BMPRII/KCNK3 signaling systems. A better understanding of novel pathways and therapeutic targets will help in the designing of new and more effective approaches for PAH treatment.
    MeSH term(s) Blood Coagulation/physiology ; Bone Morphogenetic Protein Receptors, Type II/genetics ; Bone Morphogenetic Protein Receptors, Type II/physiology ; Disease Progression ; Endothelium, Vascular/physiopathology ; Humans ; Hypertension, Pulmonary/pathology ; Hypertension, Pulmonary/physiopathology ; MicroRNAs/physiology ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/physiology ; Potassium Channels, Tandem Pore Domain/genetics ; Potassium Channels, Tandem Pore Domain/physiology ; Pulmonary Wedge Pressure ; Vascular Remodeling ; Vasodilation/physiology
    Chemical Substances MicroRNAs ; Nerve Tissue Proteins ; Potassium Channels, Tandem Pore Domain ; potassium channel subfamily K member 3 ; BMPR2 protein, human (EC 2.7.11.30) ; Bone Morphogenetic Protein Receptors, Type II (EC 2.7.11.30)
    Language English
    Publishing date 2015-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1032552-9
    ISSN 1931-3543 ; 0012-3692
    ISSN (online) 1931-3543
    ISSN 0012-3692
    DOI 10.1378/chest.14-0862
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ui III Zs.45: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 349: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Endothelial ERK1/2 signaling maintains integrity of the quiescent endothelium.

    Ricard, Nicolas / Scott, Rizaldy P / Booth, Carmen J / Velazquez, Heino / Cilfone, Nicholas A / Baylon, Javier L / Gulcher, Jeffrey R / Quaggin, Susan E / Chittenden, Thomas W / Simons, Michael

    The Journal of experimental medicine

    2019  Volume 216, Issue 8, Page(s) 1874–1890

    Abstract: To define the role of ERK1/2 signaling in the quiescent endothelium, we induced ... ...

    Abstract To define the role of ERK1/2 signaling in the quiescent endothelium, we induced endothelial
    MeSH term(s) Animals ; Deep Learning ; Disease Models, Animal ; Endothelin-1/metabolism ; Endothelium/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypertension/metabolism ; MAP Kinase Signaling System/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitogen-Activated Protein Kinase 1/genetics ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/genetics ; Mitogen-Activated Protein Kinase 3/metabolism ; Nitric Oxide Synthase Type III/metabolism ; RNA-Seq ; Transfection ; Transforming Growth Factor beta/metabolism
    Chemical Substances Endothelin-1 ; Transforming Growth Factor beta ; NOS3 protein, human (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Nos3 protein, mouse (EC 1.14.13.39) ; MAPK1 protein, human (EC 2.7.11.24) ; MAPK3 protein, human (EC 2.7.11.24) ; Mapk1 protein, mouse (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24)
    Language English
    Publishing date 2019-06-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20182151
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.107: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 45: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Bone Morphogenetic Protein 9 Is a Paracrine Factor Controlling Liver Sinusoidal Endothelial Cell Fenestration and Protecting Against Hepatic Fibrosis.

    Desroches-Castan, Agnès / Tillet, Emmanuelle / Ricard, Nicolas / Ouarné, Marie / Mallet, Christine / Belmudes, Lucid / Couté, Yohann / Boillot, Olivier / Scoazec, Jean-Yves / Bailly, Sabine / Feige, Jean-Jacques

    Hepatology (Baltimore, Md.)

    2019  Volume 70, Issue 4, Page(s) 1392–1408

    Abstract: Bone morphogenetic protein 9 (BMP9) is a circulating factor produced by hepatic stellate cells that plays a critical role in vascular quiescence through its endothelial receptor activin receptor-like kinase 1 (ALK1). Mutations in the gene encoding ALK1 ... ...

    Abstract Bone morphogenetic protein 9 (BMP9) is a circulating factor produced by hepatic stellate cells that plays a critical role in vascular quiescence through its endothelial receptor activin receptor-like kinase 1 (ALK1). Mutations in the gene encoding ALK1 cause hereditary hemorrhagic telangiectasia type 2, a rare genetic disease presenting hepatic vessel malformations. Variations of both the circulating levels and the hepatic mRNA levels of BMP9 have been recently associated with various forms of hepatic fibrosis. However, the molecular mechanism that links BMP9 with liver diseases is still unknown. Here, we report that Bmp9 gene deletion in 129/Ola mice triggers hepatic perisinusoidal fibrosis that was detectable from 15 weeks of age. An inflammatory response appeared within the same time frame as fibrosis, whereas sinusoidal vessel dilation developed later on. Proteomic and mRNA analyses of primary liver sinusoidal endothelial cells (LSECs) both revealed that the expression of the LSEC-specifying transcription factor GATA-binding protein 4 was strongly reduced in Bmp9 gene knockout (Bmp9-KO) mice as compared with wild-type mice. LSECs from Bmp9-KO mice also lost the expression of several terminal differentiation markers (Lyve1, Stab1, Stab2, Ehd3, Cd209b, eNos, Maf, Plvap). They gained CD34 expression and deposited a basal lamina, indicating that they were capillarized. Another main characteristic of differentiated LSECs is the presence of permeable fenestrae. LSECs from Bmp9-KO mice had a significantly reduced number of fenestrae. This was already observable in 2-week-old pups. Moreover, we could show that addition of BMP9 to primary cultures of LSECs prevented the loss of their fenestrae and maintained the expression levels of Gata4 and Plvap. Conclusion: Taken together, our observations show that BMP9 is a key paracrine regulator of liver homeostasis, controlling LSEC fenestration and protecting against perivascular hepatic fibrosis.
    MeSH term(s) Activin Receptors, Type II/genetics ; Animals ; Cells, Cultured ; Disease Models, Animal ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Gene Expression Regulation ; Growth Differentiation Factor 2/genetics ; Growth Differentiation Factor 2/metabolism ; Hepatic Stellate Cells/pathology ; Humans ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Proteomics ; RNA, Messenger/genetics ; Random Allocation ; Statistics, Nonparametric ; Tissue Culture Techniques/methods
    Chemical Substances Gdf2 protein, mouse ; Growth Differentiation Factor 2 ; RNA, Messenger ; Activin Receptors, Type II (EC 2.7.11.30) ; Acvrl1 protein, mouse (EC 2.7.11.30)
    Language English
    Publishing date 2019-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.30655
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1660: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top