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  1. Article ; Online: Activation of the renal GLP-1R leads to expression of

    Bjørnholm, Katrine Dahl / Ougaard, Maria Elm / Skovsted, Gry Freja / Knudsen, Lotte Bjerre / Pyke, Charles

    Endocrinology, diabetes & metabolism

    2021  Volume 4, Issue 3, Page(s) e00234

    Abstract: The GLP-1 receptor (GLP-1R) in the kidney is expressed exclusively in vascular smooth muscle cells in arteries and arterioles. Downstream effects of the activation of the renal vascular GLP-1R are elusive but may involve regulation of the renin- ... ...

    Abstract The GLP-1 receptor (GLP-1R) in the kidney is expressed exclusively in vascular smooth muscle cells in arteries and arterioles. Downstream effects of the activation of the renal vascular GLP-1R are elusive but may involve regulation of the renin-angiotensin-aldosterone system (RAAS). The expression of
    MeSH term(s) Animals ; Glucagon-Like Peptide-1 Receptor/agonists ; Kidney/metabolism ; Liraglutide/metabolism ; Liraglutide/pharmacology ; Liraglutide/therapeutic use ; Mice ; Renin/metabolism ; Renin/pharmacology ; Renin-Angiotensin System
    Chemical Substances Glucagon-Like Peptide-1 Receptor ; Liraglutide (839I73S42A) ; Renin (EC 3.4.23.15)
    Language English
    Publishing date 2021-03-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2398-9238
    ISSN (online) 2398-9238
    DOI 10.1002/edm2.234
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Shared and Distinct Renal Transcriptome Signatures in 3 Standard Mouse Models of Chronic Kidney Disease.

    Marstrand-Jørgensen, Adam B / Sembach, Frederikke Emilie / Bak, Stine Thorhauge / Ougaard, Maria / Christensen-Dalsgaard, Mikkel / Rønn Madsen, Martin / Jensen, Ditte Marie / Secher, Thomas / Heimbürger, Sebastian Møller Nguyen / Fink, Lisbeth N / Hansen, Ditte / Hansen, Henrik H / Østergaard, Mette Viberg / Christensen, Michael / Dalbøge, Louise S

    Nephron

    2024  , Page(s) 1–16

    Abstract: Introduction: Several mouse models with diverse disease etiologies are used in preclinical research for chronic kidney disease (CKD). Here, we performed a head-to-head comparison of renal transcriptome signatures in standard mouse models of CKD to ... ...

    Abstract Introduction: Several mouse models with diverse disease etiologies are used in preclinical research for chronic kidney disease (CKD). Here, we performed a head-to-head comparison of renal transcriptome signatures in standard mouse models of CKD to assess shared and distinct molecular changes in three mouse models commonly employed in preclinical CKD research and drug discovery.
    Methods: All experiments were conducted on male C57BL/6J mice. Mice underwent sham, unilateral ureter obstruction (UUO), or unilateral ischemic-reperfusion injury (uIRI) surgery and were terminated two- and 6-weeks post-surgery, respectively. The adenine-supplemented diet-induced (ADI) model of CKD was established by feeding with adenine diet for 6 weeks and compared to control diet feeding. For all models, endpoints included plasma biochemistry, kidney histology, and RNA sequencing.
    Results: All models displayed increased macrophage infiltration (F4/80 IHC) and fibrosis (collagen 1a1 IHC). Compared to corresponding controls, all models were characterized by an extensive number of renal differentially expressed genes (≥11,000), with a notable overlap in transcriptomic signatures across models. Gene expression markers of fibrosis, inflammation, and kidney injury supported histological findings. Interestingly, model-specific transcriptome signatures included several genes representing current drug targets for CKD, emphasizing advantages and limitations of the three CKD models in preclinical target and drug discovery.
    Conclusion: The UUO, uIRI, and ADI mouse models of CKD have significant commonalities in their renal global transcriptome profile. Model-specific renal transcriptional signatures should be considered when selecting the specific model in preclinical target and drug discovery.
    Language English
    Publishing date 2024-02-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 207121-6
    ISSN 2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
    ISSN (online) 2235-3186 ; 1423-0186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000535918
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 169: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  3. Article ; Online: Decreased expression of the GLP-1 receptor after segmental artery injury in mice.

    Bjørnholm, Katrine Dahl / Povlsen, Gro Klitgaard / Ougaard, Maria Elm / Pyke, Charles / Rakipovski, Günaj / Tveden-Nyborg, Pernille / Lykkesfeldt, Jens / Skovsted, Gry Freja

    The Journal of endocrinology

    2021  Volume 248, Issue 3, Page(s) 289–301

    Abstract: The glucagon-like peptide-1 receptor (GLP1R) is expressed in the renal vasculature and known to be downregulated under hypertensive conditions in rats and humans. However, little is known about the regulation in other types of renal pathology involving ... ...

    Abstract The glucagon-like peptide-1 receptor (GLP1R) is expressed in the renal vasculature and known to be downregulated under hypertensive conditions in rats and humans. However, little is known about the regulation in other types of renal pathology involving vascular changes. This study investigates the expression of the GLP1R in renal vasculature after glomerular injury in the nephrotoxic nephritis mouse model, high cholesterol, and atherosclerosis in the Ldlr-/- mouse on Western diet, and ex vivo injury in an organ culture model. The immunohistochemical signal of the GLP1R was significantly decreased in arteries from mice with nephrotoxic nephritis after 42 days compared to 7 days and saline control (P < 0.05). Histological evaluation of kidneys from Ldlr-/- mice on Western diet showed a decreased GLP1R specific immunohistochemical signal (P < 0.05). The dilatory response to liraglutide was decreased in Western diet fed Ldlr-/- mice compared to C57Bl/6J controls (P < 0.05). Organ culture significantly decreased the immunohistochemical signal of the GLP1R (P <0.05) and the expression of Glp1r mRNA (P < 0.005) compared to fresh. Organ cultured vessels showed vascular smooth muscle cell remodelling as Acta2 expression was decreased (P < 0.005) and Ednrb was increased (P < 0.05). In conclusion, nephrotoxic nephritis and hypercholesterolaemia led to decreased GLP1R specific immunohistochemical signal. Ex vivo vascular injury in the organ culture model leads to a decrease in expression of GLP1R expressionand contractile VSMC specific markers and increase in expression of dedifferentiation markers suggestive of an inverse relationship between phenotypic switch of the VSMC and the expression of the GLP1R; however, the causal relationship remains elusive.
    MeSH term(s) Animals ; Female ; Glucagon-Like Peptide-1 Receptor/metabolism ; Mice ; Nephritis/metabolism ; Organ Culture Techniques ; Renal Artery/metabolism ; Vascular Diseases/metabolism
    Chemical Substances Glp1r protein, mouse ; Glucagon-Like Peptide-1 Receptor
    Language English
    Publishing date 2021-02-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3028-4
    ISSN 1479-6805 ; 0022-0795
    ISSN (online) 1479-6805
    ISSN 0022-0795
    DOI 10.1530/JOE-20-0608
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.133: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Liraglutide Improves the Kidney Function in a Murine Model of Chronic Kidney Disease.

    Ougaard, Maria E / Sembach, Frederikke E / Jensen, Henrik E / Pyke, Charles / Knudsen, Lotte B / Kvist, Peter H

    Nephron

    2020  Volume 144, Issue 11, Page(s) 595–606

    Abstract: Background: Chronic kidney disease (CKD) is a global health burden, and the current treatment options only slow down the disease progression. GLP-1 receptor agonists (GLP-1 RA) have shown a renal protective effect in models of CKD; however, the ... ...

    Abstract Background: Chronic kidney disease (CKD) is a global health burden, and the current treatment options only slow down the disease progression. GLP-1 receptor agonists (GLP-1 RA) have shown a renal protective effect in models of CKD; however, the mechanism behind the beneficial effect is not understood. In this study, we investigate the effect of the GLP-1 RA liraglutide in the nephrotoxic serum nephritis (NTN) CKD model. Moreover, we compare the gene expression pattern of liraglutide-treated mice to the gene expression pattern of mice treated with the angiotensin converting enzyme inhibitor, enalapril.
    Methods: The effect of liraglutide was tested in the NTN model by evaluating the glomerular filtration rate (GFR), albuminuria, mesangial expansion, renal fibrosis, and renal inflammation. Furthermore, the regulation of selected genes involved in CKD and in glomerular, cortical tubulointerstitial, and whole kidney structures was analyzed using a gene expression array on samples following laser capture microdissection.
    Results: Treatment with liraglutide improved CKD hallmarks including GFR, albuminuria, mesangial expansion, renal inflammation, and renal fibrosis. The gene expression revealed that both liraglutide and enalapril reversed the regulation of several fibrosis and inflammation associated genes, which are also regulated in human CKD patients. Furthermore, liraglutide and enalapril both regulated genes in the kidney involved in blood pressure control.
    Conclusions: Treatment with liraglutide improved the kidney function and diminished renal lesions in NTN-induced mice. Both liraglutide and enalapril reversed the regulation of genes involved in CKD and regulated genes involved in blood pressure control.
    MeSH term(s) Albuminuria/drug therapy ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Animals ; Disease Models, Animal ; Gene Expression Regulation/drug effects ; Glomerular Filtration Rate/drug effects ; Humans ; Liraglutide/pharmacology ; Liraglutide/therapeutic use ; Mice ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/physiopathology
    Chemical Substances Angiotensin-Converting Enzyme Inhibitors ; Liraglutide (839I73S42A)
    Language English
    Publishing date 2020-09-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 207121-6
    ISSN 2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
    ISSN (online) 2235-3186 ; 1423-0186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000509418
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    Zs.A 169: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Spontaneous calcium waves in granule cells in cerebellar slice cultures.

    Apuschkin, Mia / Ougaard, Maria / Rekling, Jens C

    Neuroscience letters

    2013  Volume 553, Page(s) 78–83

    Abstract: Multiple regions in the CNS display propagating correlated activity during embryonic and postnatal development. This activity can be recorded as waves of increased calcium concentrations in spiking neurons or glia cells, and have been suggested to be ... ...

    Abstract Multiple regions in the CNS display propagating correlated activity during embryonic and postnatal development. This activity can be recorded as waves of increased calcium concentrations in spiking neurons or glia cells, and have been suggested to be involved in patterning, axonal guidance and establishment of synaptic transmission. Here, we used calcium imaging in slice cultures of the postnatal cerebellum, and observe spontaneous propagating calcium waves in NeuN-positive granule-like cells. Wave formation was blocked by TTX and the AMPA antagonist NBQX, but persisted after NMDA receptor blockade with MK-801. Whole-cell recordings during wave formation showed cyclic EPSP barrages with an amplitude of 10-20 mV concurrent with wave activity. Local non-propagating putative transglial waves were also present in the cultures, and could be reproduced by pressure application of ATP. We hypothesize, that the propagating wave activity is carried through the tissue by axonal collaterals formed by neighboring granule cells, and further suggest that the correlated activity may be related to processes that ensure correct postnatal wiring of the cerebellar circuits.
    MeSH term(s) Animals ; Calcium/metabolism ; Cerebellum/cytology ; Cerebellum/metabolism ; In Vitro Techniques ; Mice ; Neurons/metabolism ; Patch-Clamp Techniques ; Receptors, AMPA/metabolism ; Synaptic Transmission
    Chemical Substances Receptors, AMPA ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2013-10-11
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2013.08.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1166: Show issues Location:
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  6. Article ; Online: Temporal Regulation of Glomerular and Cortical Tubulointerstitial Genes Involved in the Development of Nephrotoxic Serum Nephritis.

    Ougaard, Maria E / Sembach, Frederikke E / Kvist, Peter H / Tonnesen, Morten / Frederiksen, Klaus S / Egfjord, Martin / Jensen, Henrik E / Galsgaard, Elisabeth D

    Nephron

    2018  Volume 140, Issue 3, Page(s) 218–230

    Abstract: Background/aims: Murine nephrotoxic nephritis (NTN) is a well-established model resembling chronic kidney disease. Investigating gene expression patterns separately in the glomerular and cortical tubulointerstitial structure could provide new knowledge ... ...

    Abstract Background/aims: Murine nephrotoxic nephritis (NTN) is a well-established model resembling chronic kidney disease. Investigating gene expression patterns separately in the glomerular and cortical tubulointerstitial structure could provide new knowledge about structure-specific changes in expression of genes in the NTN model.
    Methods: Glomerular, cortical tubulointerstitial and whole kidney tissues from mice subjected to nephrotoxic serum (NTS) or phosphate buffered saline (PBS) were collected on day 7, 21 and 42 using laser microdissection (LMD). Total RNA was extracted and subjected to nCounter NanoString. Histology, immunohistochemistry, in situ hybridization and/or quantitative real time PCR (qRT PCR) were performed to confirm regulation of selected genes.
    Results: LMD provided detailed information about genes that were regulated differently between structures over time. Some of the fibrotic and inflammatory genes (Col1a1, Col3a1 and Ccl2) were upregulated in both structures, whereas other genes such as Spp1 and Grem1 were differentially regulated suggesting spatial pathogenic mechanisms in the kidney. Downregulation of cortical tubulointerstitium genes involved in iron metabolism was detected along with iron accumulation.
    Conclusion: This study demonstrates several regulated genes in pathways important for the pathogenesis of the NTN model and that LMD identifies structure-specific changes in gene expression during disease development. Furthermore, this study shows the benefits of isolating glomeruli and cortical tubulointerstitium in order to identify gene regulation.
    MeSH term(s) Animals ; Female ; Gene Expression Regulation ; Humans ; Inflammation/genetics ; Iron/metabolism ; Kidney Cortex/metabolism ; Kidney Glomerulus/metabolism ; Mice ; Nephritis/blood ; Nephritis/chemically induced ; Nephritis/genetics
    Chemical Substances Iron (E1UOL152H7)
    Language English
    Publishing date 2018-09-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 207121-6
    ISSN 2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
    ISSN (online) 2235-3186 ; 1423-0186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000492294
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 169: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article: Temporal Regulation of Glomerular and Cortical Tubulointerstitial Genes Involved in the Development of Nephrotoxic Serum Nephritis

    Ougaard, Maria E. / Sembach, Frederikke E. / Kvist, Peter H. / Tonnesen, Morten / Frederiksen, Klaus S. / Egfjord, Martin / Jensen, Henrik E. / Galsgaard, Elisabeth D.

    Nephron

    2018  Volume 140, Issue 3, Page(s) 218–230

    Abstract: Background/Aims: Murine nephrotoxic nephritis (NTN) is a well-established model resembling chronic kidney disease. Investigating gene expression patterns separately in the glomerular and cortical tubulointerstitial structure could provide new knowledge ... ...

    Institution Novo Nordisk A/S, Måløv, Denmark
    Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark
    Department of Nephrology, Copenhagen University Hospital, Copenhagen, Denmark
    Abstract Background/Aims: Murine nephrotoxic nephritis (NTN) is a well-established model resembling chronic kidney disease. Investigating gene expression patterns separately in the glomerular and cortical tubulointerstitial structure could provide new knowledge about structure-specific changes in expression of genes in the NTN model. Methods: Glomerular, cortical tubulointerstitial and whole kidney tissues from mice subjected to nephrotoxic serum (NTS) or phosphate buffered saline (PBS) were collected on day 7, 21 and 42 using laser microdissection (LMD). Total RNA was extracted and subjected to nCounter NanoString. Histology, immunohistochemistry, in situ hybridization and/or quantitative real time PCR (qRT PCR) were performed to confirm regulation of selected genes. Results: LMD provided detailed information about genes that were regulated differently between structures over time. Some of the fibrotic and inflammatory genes (Col1a1Col3a1 and Ccl2) were upregulated in both structures, whereas other genes such as Spp1 and Grem1 were differentially regulated suggesting spatial pathogenic mechanisms in the kidney. Downregulation of cortical tubulointerstitium genes involved in iron metabolism was detected along with iron accumulation. Conclusion: This study demonstrates several regulated genes in pathways important for the pathogenesis of the NTN model and that LMD identifies structure-specific changes in gene expression during disease development. Furthermore, this study shows the benefits of isolating glomeruli and cortical tubulointerstitium in order to identify gene regulation.
    Keywords Kidney ; Laser microdissection ; Nephrotoxic nephritis ; Inflammation ; Fibrosis ; Iron
    Language English
    Publishing date 2018-09-11
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Experimental Nephrology and Genetics: Original Paper
    ZDB-ID 207121-6
    ISSN 2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
    ISSN (online) 2235-3186 ; 1423-0186
    ISSN 1660-8151 ; 0028-2766
    DOI 10.1159/000492294
    Database Karger publisher's database

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    Jg. 1995 - 2021: Lesesall (1.OG)
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