| 1. |
- Aad, G., et al.
(författare)
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- 2011
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Muller-Deile, J., et al.
(författare)
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Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases
- 2017
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538. ; 92:4, s. 836-849
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
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| 4. |
- Muller-Deile, J., et al.
(författare)
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Identification of cell and disease specific microRNAs in glomerular pathologies
- 2019
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Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 23:6, s. 3927-3939
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression in physiological processes as well as in diseases. Currently miRs are already used to find novel mechanisms involved in diseases and in the future, they might serve as diagnostic markers. To identify miRs that play a role in glomerular diseases urinary miR-screenings are a frequently used tool. However, miRs that are detected in the urine might simply be filtered from the blood stream and could have been produced anywhere in the body, so they might be completely unrelated to the diseases. We performed a combined miR-screening in pooled urine samples from patients with different glomerular diseases as well as in cultured human podocytes, human mesangial cells, human glomerular endothelial cells and human tubular cells. The miR-screening in renal cells was done in untreated conditions and after stimulation with TGF-beta. A merge of the detected regulated miRs led us to identify disease-specific, cell type-specific and cell stress-induced miRs. Most miRs were down-regulated following the stimulation with TGF-beta in all cell types. Up-regulation of miRs after TGF-beta was cell type-specific for most miRs. Furthermore, urinary miRs from patients with different glomerular diseases could be assigned to the different renal cell types. Most miRs were specifically regulated in one disease. Only miR-155 was up-regulated in all disease urines compared to control and therefore seems to be rather unspecific. In conclusion, a combined urinary and cell miR-screening can improve the interpretation of screening results. These data are useful to identify novel miRs potentially involved in glomerular diseases.
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| 5. |
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| 6. |
- Muller-Deile, J., et al.
(författare)
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Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- So far the pathomechanism of preeclampsia in pregnancy is focussed on increased circulating levels of soluble fms-like tyrosin kinase-1 (sFLT-1) that neutralizes glomerular VEGF-A expression and prevents its signaling at the glomerular endothelium. As a result of changed glomerular VEGF-A levels endotheliosis and podocyte foot process effacement are typical morphological features of preeclampsia. Recently, microRNA-26a-5p (miR-26a-5p) was described to be also upregulated in the preeclamptic placenta. We found that miR-26a-5p targets VEGF-A expression by means of PIK3C2a in cultured human podocytes and that miR-26a-5p overexpression in zebrafish causes proteinuria, edema, glomerular endotheliosis and podocyte foot process effacement. Interestingly, recombinant zebrafish Vegf-Aa protein could rescue glomerular changes induced by miR-26a-5p. In a small pilot study, preeclamptic patients with podocyte damage identified by podocyturia, expressed significantly more urinary miR-26a-5p compared to healthy controls. Thus, functional and ultrastructural glomerular changes after miR-26a-5p overexpression can resemble the findings seen in preeclampsia and indicate a potential pathophysiological role of miR-26a-5p in addition to sFLT-1 in this disease.
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| 7. |
- Muller-Deile, J., et al.
(författare)
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Overexpression of TGF-beta Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans
- 2016
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Ingår i: Cellular Physiology and Biochemistry. - : S. Karger AG. - 1015-8987 .- 1421-9778. ; 40:5, s. 819-830
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Tidskriftsartikel (refereegranskat)abstract
- 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
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| 8. |
- Dillier, N, et al.
(författare)
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Measurement of the electrically evoked compound action potential via a neural response telemetry system
- 2002
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Ingår i: Annals of Otology, Rhinology & Laryngology. - 0003-4894. ; 111:5, s. 407-414
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Tidskriftsartikel (refereegranskat)abstract
- The main aim of this study was to validate a new technique, neural response telemetry (NRT), for measuring the electrically evoked compound action potential in adult cochlear implant users via their Nucleus CI24M implant. Thirty-eight adults were evaluated with a variety of measurement procedures with the NRT software. Electrically evoked compound action potentials were obtained in 31 of the 38 adults (81.6%) and in 132 of the 160 electrodes (82.5%) tested. In addition to validating this technique, We also established a set of default clinical test parameters.
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| 9. |
- Ursu, R., et al.
(författare)
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Glomerular Endothelial Cell-Derived miR-200c Impairs Glomerular Homeostasis by Targeting Podocyte VEGF-A
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 23:23
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Tidskriftsartikel (refereegranskat)abstract
- Deciphering the pathophysiological mechanisms of primary podocytopathies that can lead to end-stage renal disease and increased mortality is an unmet need. Studying how microRNAs (miRs) interfere with various signaling pathways enables identification of pathomechanisms, novel biomarkers and potential therapeutic options. We investigated the expression of miR-200c in urine from patients with different renal diseases as a potential candidate involved in podocytopathies. The role of miR-200c for the glomerulus and its potential targets were studied in cultured human podocytes, human glomerular endothelial cells and in the zebrafish model. miR-200c was upregulated in urine from patients with minimal change disease, membranous glomerulonephritis and focal segmental glomerulosclerosis and also in transforming growth factor beta (TGF-beta) stressed glomerular endothelial cells, but not in podocytes. In zebrafish, miR-200c overexpression caused proteinuria, edema, podocyte foot process effacement and glomerular endotheliosis. Although zinc finger E-Box binding homeobox 1/2 (ZEB1/2), important in epithelial to mesenchymal transition (EMT), are prominent targets of miR-200c, their downregulation did not explain our zebrafish phenotype. We detected decreased vegfaa/bb in zebrafish overexpressing miR-200c and could further prove that miR-200c decreased VEGF-A expression and secretion in cultured human podocytes. We hypothesize that miR-200c is released from glomerular endothelial cells during cell stress and acts in a paracrine, autocrine, as well as context-dependent manner in the glomerulus. MiR-200c can cause glomerular damage most likely due to the reduction of podocyte VEGF-A. In contrast, miR-200c might also influence ZEB expression and therefore EMT, which might be important in other conditions. Therefore, we propose that miR-200c-mediated effects in the glomerulus are context-sensitive.
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