Autonomous Calcium Signaling in Human and Zebrafish Podocytes Controls Kidney Filtration Barrier Morphogenesis.

Background: Podocytes are critical to maintaining the glomerular filtration barrier, and mutations in nephrotic syndrome genes are known to affect podocyte calcium signaling. However, the role of calcium signaling during podocyte development remains unknown.

Methods: We undertook live imaging of calcium signaling in developing podocytes, using zebrafish larvae and human kidney organoids.

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

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.

Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases.

The pathophysiology of many proteinuric kidney diseases is poorly understood, and microRNAs (miRs) regulation of these diseases has been largely unexplored. Here, we tested whether miR-378a-3p is a novel regulator of glomerular diseases. MiR-378a-3p has two predicted targets relevant to glomerular function, the glomerular basement membrane matrix component, nephronectin (NPNT), and vascular endothelial growth factor VEGF-A.