ZFIN ID: ZDB-PUB-180228-4
Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish
Müller-Deile, J., Schröder, P., Beverly-Staggs, L., Hiss, R., Fiedler, J., Nyström, J., Thum, T., Haller, H., Schiffer, M.
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.
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.