1 Ocak 2019 Dergi makalesi Açık Erişim

Icli, Basak; Wu, Winona; Ozdemir, Denizhan; Li, Hao; Cheng, Henry S.; Haemmig, Stefan; Liu, Xin; Giatsidis, Giorgio; Avci, Seyma Nazli; Lee, Nathan; Guimaraes, Raphael Boesch; Manica, Andre; Marchini, Julio F.; Rynning, Stein Erik; Risnes, Ivar; Hollan, Ivana; Croce, Kevin; Yang, Xianbin; Orgill, Dennis P.; Feinberg, Mark W.

Dublin Core

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<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Icli, Basak</dc:creator>
  <dc:creator>Wu, Winona</dc:creator>
  <dc:creator>Ozdemir, Denizhan</dc:creator>
  <dc:creator>Li, Hao</dc:creator>
  <dc:creator>Cheng, Henry S.</dc:creator>
  <dc:creator>Haemmig, Stefan</dc:creator>
  <dc:creator>Liu, Xin</dc:creator>
  <dc:creator>Giatsidis, Giorgio</dc:creator>
  <dc:creator>Avci, Seyma Nazli</dc:creator>
  <dc:creator>Lee, Nathan</dc:creator>
  <dc:creator>Guimaraes, Raphael Boesch</dc:creator>
  <dc:creator>Manica, Andre</dc:creator>
  <dc:creator>Marchini, Julio F.</dc:creator>
  <dc:creator>Rynning, Stein Erik</dc:creator>
  <dc:creator>Risnes, Ivar</dc:creator>
  <dc:creator>Hollan, Ivana</dc:creator>
  <dc:creator>Croce, Kevin</dc:creator>
  <dc:creator>Yang, Xianbin</dc:creator>
  <dc:creator>Orgill, Dennis P.</dc:creator>
  <dc:creator>Feinberg, Mark W.</dc:creator>
  <dc:date>2019-01-01</dc:date>
  <dc:description>Objective- In response to tissue injury, the appropriate progression of events in angiogenesis is controlled by a careful balance between pro and antiangiogenic factors. We aimed to identify and characterize microRNAs that regulate angiogenesis in response to tissue injury. Approach and Results- We show that in response to tissue injury, microRNA-615-5p (miR-615-5p) is rapidly induced and serves as an antiangiogenic microRNA by targeting endothelial cell VEGF (vascular endothelial growth factor)-AKT (protein kinase B)/eNOS (endothelial nitric oxide synthase) signaling in vitro and in vivo. MiR-615-5p expression is increased in wounds of diabetic db/db mice, in plasma of human subjects with acute coronary syndromes, and in plasma and skin of human subjects with diabetes mellitus. Ectopic expression of miR-615-5p markedly inhibited endothelial cell proliferation, migration, network tube formation in Matrigel, and the release of nitric oxide, whereas miR-615-5p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3 ' untranslated region reporter and microribonucleoprotein immunoprecipitation assays, and small interfering RNA dependency studies demonstrate that miR-615-5p inhibits the VEGF-AKT/eNOS signaling pathway in endothelial cells by targeting IGF2 (insulin-like growth factor 2) and RASSF2 (Ras-associating domain family member 2). Local delivery of miR-615-5p inhibitors, markedly increased angiogenesis, granulation tissue thickness, and wound closure rates in db/db mice, whereas miR-615-5p mimics impaired these effects. Systemic miR-615-5p neutralization improved skeletal muscle perfusion and angiogenesis after hindlimb ischemia in db/db mice. Finally, modulation of miR-615-5p expression dynamically regulated VEGF-induced AKT signaling and angiogenesis in human skin organoids as a model of tissue injury. Conclusions- These findings establish miR-615-5p as an inhibitor of VEGF-AKT/eNOS-mediated endothelial cell angiogenic responses and that manipulating miR-615-5p expression could provide a new target for angiogenic therapy in response to tissue injury.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/112080</dc:identifier>
  <dc:identifier>oai:zenodo.org:112080</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 39(7) 1458-1474</dc:source>
  <dc:title>MicroRNA-615-5p Regulates Angiogenesis and Tissue Repair by Targeting AKT/eNOS (Protein Kinase B/Endothelial Nitric Oxide Synthase) Signaling in Endothelial Cells</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>