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Overexpression of T...
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Muller-Deile, J.
(författare)
Overexpression of TGF-beta Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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2016-12-07
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S. Karger AG,2016
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/250060
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https://gup.ub.gu.se/publication/250060URI
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https://doi.org/10.1159/000453142DOI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Background: TGF-alpha 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-alpha. Since miR-143-3p (miR-143) is described as a TGF-alpha 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-alpha. 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-alpha 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. (C) 2016 The Author(s) Published by S. Karger AG, Basel
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Gellrich, F.
(författare)
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Schenk, H.
(författare)
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Schroder, P.
(författare)
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Nyström, Jenny,1972Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xnysje
(författare)
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Lorenzen, J.
(författare)
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Haller, H.
(författare)
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Schiffer, M.
(författare)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för fysiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cellular Physiology and Biochemistry: S. Karger AG40:5, s. 819-8301015-89871421-9778
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