Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish.

Abstract

So far the pathomechanism of preeclampsia in pregnancy is focussed on increased circulating levels of soluble fms-like tyrosin kinase-1 (sFLT-1) that neutralizes glomerular VEGF-A expression and prevents its signaling at the glomerular endothelium. As a result of changed glomerular VEGF-A levels endotheliosis and podocyte foot process effacement are typical morphological features of preeclampsia. Recently, microRNA-26a-5p (miR-26a-5p) was described to be also upregulated in the preeclamptic placenta. We found that miR-26a-5p targets VEGF-A expression by means of PIK3C2α in cultured human podocytes and that miR-26a-5p overexpression in zebrafish causes proteinuria, edema, glomerular endotheliosis and podocyte foot process effacement. Interestingly, recombinant zebrafish Vegf-Aa protein could rescue glomerular changes induced by miR-26a-5p. In a small pilot study, preeclamptic patients with podocyte damage identified by podocyturia, expressed significantly more urinary miR-26a-5p compared to healthy controls. Thus, functional and ultrastructural glomerular changes after miR-26a-5p overexpression can resemble the findings seen in preeclampsia and indicate a potential pathophysiological role of miR-26a-5p in addition to sFLT-1 in this disease.

• Authors: Janina Müller-Deile, Patricia Schröder, Lynne Beverly-Staggs, Rebecca Hiss, Jan Fiedler, Jenny Nyström, Thomas Thum, Hermann Haller, Mario Schiffer
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 3621 (02 26 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29483572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs

Topics

• Animals
• Cells, Cultured
• Female
• Humans
• MicroRNAs (genetics, metabolism)
• Podocytes (metabolism)
• Pre-Eclampsia (genetics, metabolism)
• Pregnancy
• Proteinuria (etiology, metabolism)
• Zebrafish