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WFRF:(Petrova Tatiana V.)
 

Sökning: WFRF:(Petrova Tatiana V.) > FOXC2 and fluid she...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004937naa a2200505 4500
001oai:DiVA.org:uu-265686
003SwePub
008151102s2015 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2656862 URI
0247 a https://doi.org/10.1172/JCI804542 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Sabine, Amelieu CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.4 aut
2451 0a FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature
264 1c 2015
338 a print2 rdacarrier
520 a Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
7001 a Bovay, Estheru CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.4 aut
7001 a Demir, Cansaran Saygiliu CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.4 aut
7001 a Kimura, Wataruu Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan.4 aut
7001 a Jaquet, Murielu CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.4 aut
7001 a Agalarov, Yanu CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.4 aut
7001 a Zangger, Nadineu SIB, Lausanne, Switzerland.4 aut
7001 a Scallan, Joshua P.u Univ Missouri, Columbia, MO USA.4 aut
7001 a Graber, Werneru Univ Bern, Inst Anat, Bern, Switzerland.4 aut
7001 a Gulpinar, Elginu Harvard Univ, Cambridge, MA USA.4 aut
7001 a Kwak, Brenda R.u Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland.;Univ Geneva, Dept Med Specializat Cardiol, Geneva, Switzerland.4 aut
7001 a Mäkinen, Taijau Uppsala universitet,Vaskulärbiologi4 aut0 (Swepub:uu)taima352
7001 a Martinez-Corral, Inesu Spanish Natl Canc Res Ctr, Madrid, Spain.4 aut
7001 a Ortega, Sagrariou Spanish Natl Canc Res Ctr, Madrid, Spain.4 aut
7001 a Delorenzi, Maurou SIB, Lausanne, Switzerland.;Univ Lausanne, Ludwig Ctr Canc Res, Lausanne, Switzerland.4 aut
7001 a Kiefer, Friedemannu Max Planck Inst Mol Biomed, D-48149 Munster, Germany.4 aut
7001 a Davis, Michael J.u Univ Missouri, Columbia, MO USA.4 aut
7001 a Djonov, Valentinu Univ Bern, Inst Anat, Bern, Switzerland.4 aut
7001 a Miura, Naoyuldu Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan.4 aut
7001 a Petrova, Tatiana V.u CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.;Ecole Polytech Fed Lausanne, Swiss Canc Res Inst, Lausanne, Switzerland.4 aut
7102 a CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.b Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan.4 org
7730 t Journal of Clinical Investigationg 125:10, s. 3861-3877q 125:10<3861-3877x 0021-9738x 1558-8238
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-265686
8564 8u https://doi.org/10.1172/JCI80454

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