PUBLICATION
Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish
- Authors
- Müller-Deile, J., Schröder, P., Beverly-Staggs, L., Hiss, R., Fiedler, J., Nyström, J., Thum, T., Haller, H., Schiffer, M.
- ID
- ZDB-PUB-180228-4
- Date
- 2018
- Source
- Scientific Reports 8: 3621 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cells, Cultured
- Female
- Humans
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Podocytes/metabolism
- Pre-Eclampsia/genetics
- Pre-Eclampsia/metabolism*
- Pregnancy
- Proteinuria/etiology*
- Proteinuria/metabolism*
- Zebrafish
- PubMed
- 29483572 Full text @ Sci. Rep.
Citation
Müller-Deile, J., Schröder, P., Beverly-Staggs, L., Hiss, R., Fiedler, J., Nyström, J., Thum, T., Haller, H., Schiffer, M. (2018) Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish. Scientific Reports. 8:3621.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping