Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases
Müller-Deile J, Dannenberg J, Schroder P, Lin MH, Miner JH, Chen R, Braesen JH, Thum T, Nystrom J, Staggs LB, Haller H, Fiedler J, Lorenzen JM, Schiffer M (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 92
Pages Range: 836-849
Journal Issue: 4
DOI: 10.1016/j.kint.2017.03.005
Abstract
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. In zebrafish (Danio rerio), miR-378a-3p mimic injection or npnt knockdown by a morpholino oligomer caused an identical phenotype consisting of edema, proteinuria, podocyte effacement, and widening of the glomerular basement membrane in the lamina rara interna. Zebrafish vegf-A protein could not rescue this phenotype. However, mouse Npnt constructs containing a mutated 3'UTR region prevented the phenotype caused by miR-378a-3p mimic injection. Overexpression of miR-378a-3p in mice confirmed glomerular dysfunction in a mammalian model. Biopsies from patients with focal segmental glomerulosclerosis and membranous nephropathy had increased miR-378a-3p expression and reduced glomerular levels of NPNT. Thus, miR-378a-3p-mediated suppression of the glomerular matrix protein NPNT is a novel mechanism for proteinuria development in active glomerular diseases.
Authors with CRIS profile
Additional Organisation(s)
Involved external institutions
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Germany (DE)
Washington University
United States (USA) (US)
Mount Desert Island Biological Laboratory
United States (USA) (US)
University of Gothenburg / Göteborgs universitet
Sweden (SE)
Germany (DE)
Washington University
United States (USA) (US)
Mount Desert Island Biological Laboratory
United States (USA) (US)
University of Gothenburg / Göteborgs universitet
Sweden (SE)
How to cite
APA:
Müller-Deile, J., Dannenberg, J., Schroder, P., Lin, M.-H., Miner, J.H., Chen, R.,... Schiffer, M. (2017). Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases. Kidney International, 92(4), 836-849. https://doi.org/10.1016/j.kint.2017.03.005
MLA:
Müller-Deile, Janina, et al. "Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases." Kidney International 92.4 (2017): 836-849.
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