MicroRNA-126 prevents endothelial to mesenchymal transition and is downregulated in fibrosis

ABSTRACT NUMBER: NESS_5

 

AUTHORS
Samuel Tingle, Nina Jordan, Lucy Bates, Katie Cooke, Emily Thompson, Helen M Arthur, Colin Wilson, Neil Sheerin, Simi Ali

CORRESPONDING AUTHOR CONTACT EMAIL
moc.liamg@elgnitsemajmaS

MAIN ABSTRACT TEXT
Background: Chronic allograft dysfunction, underpinned by progressive fibrosis, remains a major hurdle in renal transplantation. There is a growing body of research demonstrating the key role of endothelial to mesenchymal transition (endMT) in fibrosis. However, the role of microRNAs in this process is poorly understood. MiR-126 is expressed in renal endothelial cells, and promotes vascular integrity. This project aimed to investigate the role of miR-126 in endMT.

Methods
Human umbilical vein endothelial cells (HUVEC) were treated with TGF-β and IL-1β to model endMT in vitro. Mouse unilateral ureteric obstruction (UUO) was used to model fibrosis in vivo (n=12). Non-cancerous poles of kidneys removed for renal cancer were screened to generate cohorts of fibrotic and non-fibrotic human renal tissue (n=6).

Results
miR-126 was downregulated over the course of in vitro endMT. Following UUO, fibrotic mouse kidneys displayed significantly lower expression of miR-126 than contralateral ‘normal’ kidneys (P=0.003). Human renal tissue displaying histological fibrosis showed significantly lower expression of miR-126 when compared to non-fibrotic tissue (P=0.01). We then introduced mimics into our in vitro model. miR-126 mimics prevented endMT of HUVECs treated with TGF-β and IL-1β, and resulted in significantly higher levels of endothelial marker CD31 ( P<0.001).

Conclusion
EndMT is known to be a key process in fibrosis. We have shown that miR-126 is downregulated during in vitro endMT, and also in renal fibrosis across multiple species. In addition, miR-126 mimics prevented endMT in vitro, indicating a possible therapeutic role in fibrosis.