scholarly journals RNA binding protein and microRNA control of endothelial cell function

2019 ◽  
Vol 115 (12) ◽  
pp. 1690-1691
Author(s):  
Arianna Felicetta ◽  
Gianluigi Condorelli
Circulation ◽  
2019 ◽  
Vol 139 (1) ◽  
pp. 101-114 ◽  
Author(s):  
Sofia-Iris Bibli ◽  
Jiong Hu ◽  
Fragiska Sigala ◽  
Ilka Wittig ◽  
Juliana Heidler ◽  
...  

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Aikaterini Gatsiou ◽  
Federica F Lunella ◽  
Carolin Amrhein ◽  
Stefan Guenther ◽  
Claudia Garcia Gonzalez ◽  
...  

Background: RNA binding proteins (RBPs) are key players in posttranscriptional regulation of mRNAs. Adenosine deaminase acting on RNA-2 (ADAR2) enzyme binds to double-stranded RNAs and controls brain development. The role of ADAR2 in endothelial cell function has not been described so far. Methods and Results: ADAR2 is expressed in human and murine endothelial cells and is 2-fold induced by hypoxia or hind limb ischemia in mice (P<0.05 for all). ADAR2 deficiency resulted in 73±12% impairment of leukocyte infiltration, in 53±4% reduced neovascularization, and a 40±6% decreased blood-flow recovery of ischemic muscle tissues in a hindlimb ischemia mouse model (P<0.001 for all). Mechanistically, ADAR2 knockdown causes a 2-fold downregulation of 522 transcripts, whereas 113 transcripts are found to be upregulated in RNA-seq experiments. Among the endothelial cell enriched, highly ADAR2-regulated transcripts was interleukin-6 signal transducer (IL6ST also known as glycoprotein-130, gp130), the receptor of interleukin-6 (IL-6). Silencing of ADAR2 resulted in a downregulation of gp130 mRNA and protein expression in endothelial cells by 65±5% and 50±5%, respectively (P<0.001 for both). Similarly, the expression of gp130 mRNA was decreased by 50±25% (P<0.05) in murine lung endothelial cells, which derived from transgenic ADAR2-null mice. Silencing of ADAR2 reduced by at least 2-fold the IL-6-mediated STAT3 phosphorylation, the mRNA expression of the IL-6-induced downstream genes MCP-1, VCAM-1 and E-selectin, and the IL-6-induced platelet and leukocyte adhesion on endothelial cells and endothelial cell network formation (P<0.05 for all). Of interest, ADAR2 regulated gp130 mRNA stability. Co-silencing of ADAR2 and Drosha completely restored the ADAR2-regulated gp130 mRNA expression indicating that ADAR2 regulates the maturation of specific microRNAs (miRs). Indeed, ADAR2 regulates by at least 2-fold the expression of 20 microRNAs, including of miR-579 and miR-320e, which are predicted to bind to the 3’-untranslated region of IL6ST mRNA. Conclusions: This study shows for the first time that ADAR2 controls miR biogenesis and thus IL-6/STAT3 signalling in endothelial cells.


2019 ◽  
Vol 157 (3) ◽  
pp. 731-743 ◽  
Author(s):  
Lan Xiao ◽  
Xiao-Xue Li ◽  
Hee Kyoung Chung ◽  
Sudhakar Kalakonda ◽  
Jia-Zhong Cai ◽  
...  

2007 ◽  
Vol 177 (4S) ◽  
pp. 78-79
Author(s):  
Lioudmila Sitnikova ◽  
Gary Mendese ◽  
Qin Lui ◽  
Bruce A. Woda ◽  
Di Lu ◽  
...  

2019 ◽  
Author(s):  
Benjamin Rauwel ◽  
Yannick Degboe ◽  
Katy Diallo ◽  
Souraya Sayegh ◽  
Michel Baron ◽  
...  

2014 ◽  
Author(s):  
Jessie M Sutherland ◽  
Alexander P Sobinoff ◽  
Kate Redgrove ◽  
Tara-Lynne Davidson ◽  
Nicole A Siddall ◽  
...  

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