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The Zebrafish Model to Study the Role of microRNAs in Glomerular Function and Disease

Janina Müller-Deile* and Mario Schiffer

microRNAs (miRs) are non-coding small RNAs that play an important role in posttranscriptional regulation of gene expression. Recent studies indicate that miRs are also mediators in different disease processes. Here we review how the zebrafish model can be used to study the role of miRs in glomerular function and disease. Microinjections of miR mimics were done in zebrafish eggs and larvae. A transgenic zebrafish line which expresses a green fluorescent plasma protein was used to investigate protein loss though the glomerular filtration barrier. Electron microscopy analysis revealed the level and degree of glomerular damage after miR overexpression. MiR- 143-3p seems to be important for glomerular glycocalyx as overexpression of miR-143-3p leads to down regulation of versican, proteinuria and damage on the endothelial and epithelial side of the glomerular filtration barrier. In contrast, overexpression of miR-378a-3p by injection of a specific miR mimic caused proteinuria, edema, podocyte effacement and thickening of the glomerular basement membrane. These findings could be rescued by coinjections of a nephronectin construct with a mutated 3’UTR region where the miR could not bind. Thus, miR mimics can be used in the zebrafish model to study the role of miRs involved in glomerular diseases.