Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans
| Title: | Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans |
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| Authors: | Janina Müller-Deile, Finn Gellrich, Heiko Schenk, Patricia Schroder, Jenny Nyström, Johan Lorenzen, Hermann Haller, Mario Schiffer |
| Source: | Cellular Physiology and Biochemistry, Vol 40, Iss 5, Pp 819-830 (2016) |
| Publisher Information: | Cell Physiol Biochem Press GmbH & Co KG, 2016. |
| Publication Year: | 2016 |
| Collection: | LCC:Physiology LCC:Biochemistry |
| Subject Terms: | Versican, Syndecan, Glycocalyx, micro-RNA-143, Podocytes, Zebrafish, Proteinuria, Glomerulus, Physiology, QP1-981, Biochemistry, QD415-436 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1015-8987 1421-9778 00045314 |
| Relation: | http://www.karger.com/Article/FullText/453142; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000453142 |
| Access URL: | https://doaj.org/article/824f8384db644a529ddc3a682265cda1 |
| Accession Number: | edsdoj.824f8384db644a529ddc3a682265cda1 |
| Database: | Directory of Open Access Journals |
| ISSN: | 10158987 14219778 00045314 |
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| DOI: | 10.1159/000453142 |
| Published in: | Cellular Physiology and Biochemistry |
| Language: | English |