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Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusivel...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069688/ https://www.ncbi.nlm.nih.gov/pubmed/27759104 http://dx.doi.org/10.1038/srep35400 |
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author | Koehler, Sybille Brähler, Sebastian Kuczkowski, Alexander Binz, Julia Hackl, Matthias J. Hagmann, Henning Höhne, Martin Vogt, Merly C. Wunderlich, Claudia M. Wunderlich, F. Thomas Schweda, Frank Schermer, Bernhard Benzing, Thomas Brinkkoetter, Paul T. |
author_facet | Koehler, Sybille Brähler, Sebastian Kuczkowski, Alexander Binz, Julia Hackl, Matthias J. Hagmann, Henning Höhne, Martin Vogt, Merly C. Wunderlich, Claudia M. Wunderlich, F. Thomas Schweda, Frank Schermer, Bernhard Benzing, Thomas Brinkkoetter, Paul T. |
author_sort | Koehler, Sybille |
collection | PubMed |
description | Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca(2+) levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca(2+) peaks on podocyte biology in living animals. Activation of the engineered G-protein coupled receptor with the synthetic compound clozapine-N-oxide (CNO) evoked a short and transient Ca(2+) peak in podocytes immediately after CNO administration in vivo. Interestingly, this Ca(2+) peak did neither affect glomerular perfusion nor filtration in the animals. Moreover, no obvious alterations in the glomerular morphology could be observed. Taken together, these in vivo findings suggest that chronic alterations and calcium overload rather than an induction of transient Ca(2+) peaks contribute to podocyte disease. |
format | Online Article Text |
id | pubmed-5069688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50696882016-10-26 Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion Koehler, Sybille Brähler, Sebastian Kuczkowski, Alexander Binz, Julia Hackl, Matthias J. Hagmann, Henning Höhne, Martin Vogt, Merly C. Wunderlich, Claudia M. Wunderlich, F. Thomas Schweda, Frank Schermer, Bernhard Benzing, Thomas Brinkkoetter, Paul T. Sci Rep Article Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca(2+) levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca(2+) peaks on podocyte biology in living animals. Activation of the engineered G-protein coupled receptor with the synthetic compound clozapine-N-oxide (CNO) evoked a short and transient Ca(2+) peak in podocytes immediately after CNO administration in vivo. Interestingly, this Ca(2+) peak did neither affect glomerular perfusion nor filtration in the animals. Moreover, no obvious alterations in the glomerular morphology could be observed. Taken together, these in vivo findings suggest that chronic alterations and calcium overload rather than an induction of transient Ca(2+) peaks contribute to podocyte disease. Nature Publishing Group 2016-10-19 /pmc/articles/PMC5069688/ /pubmed/27759104 http://dx.doi.org/10.1038/srep35400 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Koehler, Sybille Brähler, Sebastian Kuczkowski, Alexander Binz, Julia Hackl, Matthias J. Hagmann, Henning Höhne, Martin Vogt, Merly C. Wunderlich, Claudia M. Wunderlich, F. Thomas Schweda, Frank Schermer, Bernhard Benzing, Thomas Brinkkoetter, Paul T. Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion |
title | Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion |
title_full | Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion |
title_fullStr | Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion |
title_full_unstemmed | Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion |
title_short | Single and Transient Ca(2+) Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion |
title_sort | single and transient ca(2+) peaks in podocytes do not induce changes in glomerular filtration and perfusion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069688/ https://www.ncbi.nlm.nih.gov/pubmed/27759104 http://dx.doi.org/10.1038/srep35400 |
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