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

Müller-Deile J, Schroeder P, Beverly-Staggs L, Hiss R, Fiedler J, Nystroem J, Thum T, Haller H, Schiffer M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 8

Journal Issue: 1

DOI: 10.1038/s41598-018-22070-w

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 with CRIS profile

Janina Müller-Deile
Mario Schiffer

Additional Organisation(s)

Lehrstuhl für Innere Medizin IV

Involved external institutions

Mount Desert Island Biological Laboratory US United States (USA) (US) University of Gothenburg / Göteborgs universitet SE Sweden (SE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

APA:

Müller-Deile, J., Schroeder, P., Beverly-Staggs, L., Hiss, R., Fiedler, J., Nystroem, J.,... Schiffer, M. (2018). Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-22070-w

MLA:

Müller-Deile, Janina, et al. "Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish." Scientific Reports 8.1 (2018).

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