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Badacze z Biobanku Zakładu Medycznej Diagnostyki Laboratoryjnej Gdańskiego Uniwersytetu Medycznego wchodzącego w skład konsorcjum BBMRI.pl we współpracy z University of Illinois at Urbana-Champaign, University of Alabama at Birmingham, Beckman Institute of Advanced Science oraz Zakładem Biologii i Botaniki Farmaceutycznej GUMed badali rolę microRNA w redukcji ekspresji eNOS w komórkach sródbłonka w warunkach hipoksji. Udowodnili, że miR-200b reguluje ekspresję eNOS linii HUVEC w warunkach hipoksji, a wyniki zostały opublikowane w w artykule "eNOS expression and NO release during hypoxia is inhibited by miR-200b in human endothelial cells" w majowym wydaniu Angiogenesis (IF = 4.351). Zapraszamy do lektury.

 

 

Janaszak-Jasiecka A1, Siekierzycka A2, Bartoszewska S3, Serocki M4, Dobrucki LW2,5,6,7, Collawn JF8, Kalinowski L2,7, Bartoszewski R9

 
1 Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Hallera 107, 80-416, Gdańsk, Poland. Ten adres pocztowy jest chroniony przed spamowaniem. Aby go zobaczyć, konieczne jest włączenie w przeglądarce obsługi JavaScript..
2 Department of Medical Laboratory Diagnostics and Central Bank of Frozen Tissues & Genetic Specimens, Medical University of Gdansk, Gdańsk, Poland.
3 Department of Inorganic Chemistry, Medical University of Gdansk, Gdańsk, Poland.
4 Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Hallera 107, 80-416, Gdańsk, Poland.
5 Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
6 Beckman Institute for Advanced Science and Technology, Urbana, IL, USA.
7 Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Gdańsk, Poland.
8 Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, USA.
9 Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Hallera 107, 80-416, Gdańsk, Poland. Ten adres pocztowy jest chroniony przed spamowaniem. Aby go zobaczyć, konieczne jest włączenie w przeglądarce obsługi JavaScript..

 

 Abstract

The nitric oxide (NO) secreted by vascular endothelium is required for the maintenance of cardiovascular homeostasis. Diminished release of NO generated by endothelial NO synthase contributes to endothelial dysfunction. Hypoxia and ischemia reduce endothelial eNOS expression via posttranscriptional mechanisms that result in NOS3 transcript destabilization. Here, we examine whether microRNAs contribute to this mechanism. We followed the kinetics of hypoxia-induced changes in NOS3 mRNA and eNOS protein levels in primary human umbilical vein endothelial cells (HUVECs). Utilizing in silico predictive protocols to identify potential miRNAs that regulate eNOS expression, we identified miR-200b as a candidate. We established the functional miR-200b target sequence within the NOS3 3'UTR, and demonstrated that manipulation of the miRNA levels during hypoxia using miR-200b mimics and antagomirs regulates eNOS levels, and established that miR-200b physiologically limits eNOS expression during hypoxia. Furthermore, we demonstrated that the specific ablation of the hypoxic induction of miR-200b in HUVECs restored eNOS-driven hypoxic NO release to the normoxic levels. To determine whether miR-200b might be the only miRNA that had this effect, we utilized Next Generation Sequencing (NGS) to follow hypoxia-induced changes in the miRNA levels in HUVECS and found 83 novel hypoxamiRs, with two candidate miRNAs besides miR-200b that could potentially influence eNOS levels. Taken together, the data establish miR-200b-eNOS regulation as a first hypoxamiR-based mechanism that limits NO bioavailability during hypoxia in endothelial cells, and show that hypoxamiRs could become useful therapeutic targets for cardiovascular diseases and other hypoxic-related diseases including various types of cancer.