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Status: Bibliographieeintrag

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Verfasst von:Sen, Anagha [VerfasserIn]   i
 Ren, Shumei [VerfasserIn]   i
 Lerchenmüller, Carolin [VerfasserIn]   i
 Sun, Jianxin [VerfasserIn]   i
 Weiss, Norbert [VerfasserIn]   i
 Most, Patrick [VerfasserIn]   i
 Peppel, Karsten [VerfasserIn]   i
Titel:MicroRNA-138 regulates hypoxia-induced endothelial cell dysfunction by targeting S100A1
Verf.angabe:Anagha Sen, Shumei Ren, Carolin Lerchenmüller, Jianxin Sun, Norbert Weiss, Patrick Most, Karsten Peppel
E-Jahr:2013
Jahr:November 11, 2013
Umfang:10 S.
Teil:volume:8
 year:2013
 number:11
 elocationid:e78684
 pages:1-10
 extent:10
Fussnoten:Gesehen am 19.08.2021
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2013
Band/Heft Quelle:8(2013), 11, Artikel-ID e78684, Seite 1-10
ISSN Quelle:1932-6203
Abstract:The Ca2+ sensor S100A1 is essential for proper endothelial cell (EC) nitric oxide (NO) synthase (eNOS) activation. S100A1 levels are greatly reduced in primary human microvascular ECs subjected to hypoxia, rendering them dysfunctional. However mechanisms that regulate S100A1 levels in ECs are unknown. Here we show that ECs transfected with a S100A1-3′ untranslated region (UTR) luciferase reporter construct display significantly reduced gene expression when subjected to low oxygen levels or chemical hypoxia. Bioinformatic analysis suggested that microRNA -138 (MiR-138) could target the 3′UTR of S100A1. Patients with critical limb ischemia (CLI) or mice subjected to femoral artery resection (FAR) displayed increased MiR-138 levels and decreased S100A1 protein expression. Consistent with this finding, hypoxia greatly increased MiR-138 levels in ECs, but not in skeletal muscle C2C12 myoblasts or differentiated myotubes or primary human vascular smooth muscle cells. Transfection of a MiR-138 mimic into ECs reduced S100A1-3 ‘UTR reporter gene expression, while transfection of an anti MiR-138 prevented the hypoxia-induced downregulation of the reporter gene. Deletion of the 22 nucleotide putative MiR-138 target site abolished the hypoxia-induced loss of reporter gene expression. Knockdown of Hif1-α mediated by siRNA prevented loss of hypoxia-induced reporter gene expression. Conversely, specific activation of Hif1-α by a selective prolyl-hydroxylase inhibitor (IOX2) reduced reporter gene expression even in the absence of hypoxia. Finally, primary ECs transfected with a MiR-138 mimic displayed reduced tube formation when plated onto Matrigel matrix and expressed less NO when stimulated with VEGF. These effects were reversed by gene transfer of S100A1 using recombinant adenovirus. We conclude that hypoxia-induced MiR-138 is an essential mediator of EC dysfunction via its ability to target the 3′UTR of S100A1.
DOI:doi:10.1371/journal.pone.0078684
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1371/journal.pone.0078684
 Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078684
 DOI: https://doi.org/10.1371/journal.pone.0078684
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Endothelial cells
 Gene expression
 Hypoxia
 Luciferase
 Medical hypoxia
 MicroRNAs
 Reporter genes
 Transfection
K10plus-PPN:1767332203
Verknüpfungen:→ Zeitschrift

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