Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans

Müller-Deile J, Gellrich F, Schenk H, Schroder P, Nystrom J, Lorenzen J, Haller H, Schiffer M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Cellular Physiology and Biochemistry Karger

Book Volume: 40

Pages Range: 819-830

Journal Issue: 5

DOI: 10.1159/000453142

Abstract

BACKGROUND: TGF-β is known as an important stress factor of podocytes in glomerular diseases. Apart from activation of direct pro-apoptotic pathways we wanted to analyze micro-RNA (miRs) driven regulation of components involved in the integrity of the glomerular filtration barrier induced by TGF-β. Since miR-143-3p (miR-143) is described as a TGF-β inducible miR in other cell types, we examined this specific miR and its ability to induce glomerular pathology. METHODS: We analyzed miR-143 expression in cultured human podocytes after stimulation with TGF-β. We also microinjected zebrafish eggs with a miR-143 mimic or with morpholinos specific for its targets syndecan and versican and compared phenotype and proteinuria development. RESULTS: We detected a time dependent, TGF-β inducible expression of miR-143 in human podocytes. Targets of miR-143 relevant in glomerular biology are syndecans and versican, which are known components of the glycocalyx. We found that syndecan 1 and 4 were predominantly expressed in podocytes while syndecan 3 was largely expressed in glomerular endothelial cells. Versican could be detected in both cell types. After injection of a miR-143 mimic in zebrafish larvae, syndecan 3, 4 and versican were significantly downregulated. Moreover, miR-143 overexpression or versican knockdown by morpholino caused loss of plasma proteins, edema, podocyte effacement and endothelial damage. In contrast, knockdown of syndecan 3 and syndecan 4 had no effects on glomerular filtration barrier. CONCLUSION: Expression of versican and syndecan isoforms is indispensable for proper barrier function. Podocyte-derived miR-143 is a mediator for paracrine and autocrine cross talk between podocytes and glomerular endothelial cells and can alter expression of glomerular glycocalyx proteins.

Authors with CRIS profile

Janina Müller-Deile
Mario Schiffer

Additional Organisation(s)

Lehrstuhl für Innere Medizin IV

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) University of Gothenburg / Göteborgs universitet SE Sweden (SE) Mount Desert Island Biological Laboratory US United States (USA) (US)

How to cite

APA:

Müller-Deile, J., Gellrich, F., Schenk, H., Schroder, P., Nystrom, J., Lorenzen, J.,... Schiffer, M. (2016). Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans. Cellular Physiology and Biochemistry, 40(5), 819-830. https://doi.org/10.1159/000453142

MLA:

Müller-Deile, Janina, et al. "Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans." Cellular Physiology and Biochemistry 40.5 (2016): 819-830.

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