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Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death

Podocytes are critical for the maintenance of kidney ultrafiltration barrier and play a key role in the progression of glomerular diseases. Although mediator complex proteins have been shown to be important for many physiological and pathological processes, their role in kidney tissue has not been s...

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Autores principales: Rodriguez, Patricia Q., Unnersjö-Jess, David, Zambrano, Sonia S., Guo, Jing, Möller-Hackbarth, Katja, Blom, Hans, Jahnukainen, Timo, Ebarasi, Lwaki, Patrakka, Jaakko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676236/
https://www.ncbi.nlm.nih.gov/pubmed/33208756
http://dx.doi.org/10.1038/s41598-020-76870-0
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author Rodriguez, Patricia Q.
Unnersjö-Jess, David
Zambrano, Sonia S.
Guo, Jing
Möller-Hackbarth, Katja
Blom, Hans
Jahnukainen, Timo
Ebarasi, Lwaki
Patrakka, Jaakko
author_facet Rodriguez, Patricia Q.
Unnersjö-Jess, David
Zambrano, Sonia S.
Guo, Jing
Möller-Hackbarth, Katja
Blom, Hans
Jahnukainen, Timo
Ebarasi, Lwaki
Patrakka, Jaakko
author_sort Rodriguez, Patricia Q.
collection PubMed
description Podocytes are critical for the maintenance of kidney ultrafiltration barrier and play a key role in the progression of glomerular diseases. Although mediator complex proteins have been shown to be important for many physiological and pathological processes, their role in kidney tissue has not been studied. In this study, we identified a mediator complex protein 22 (Med22) as a renal podocyte cell-enriched molecule. Podocyte-specific Med22 knockout mouse showed that Med22 was not needed for normal podocyte maturation. However, it was critical for the maintenance of podocyte health as the mice developed progressive glomerular disease and died due to renal failure. Detailed morphological analyses showed that Med22-deficiency in podocytes resulted in intracellular vacuole formation followed by podocyte loss. Moreover, Med22-deficiency in younger mice promoted the progression of glomerular disease, suggesting Med22-mediated processes may have a role in the development of glomerulopathies. This study shows for the first time that mediator complex has a critical role in kidney physiology.
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spelling pubmed-76762362020-11-23 Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death Rodriguez, Patricia Q. Unnersjö-Jess, David Zambrano, Sonia S. Guo, Jing Möller-Hackbarth, Katja Blom, Hans Jahnukainen, Timo Ebarasi, Lwaki Patrakka, Jaakko Sci Rep Article Podocytes are critical for the maintenance of kidney ultrafiltration barrier and play a key role in the progression of glomerular diseases. Although mediator complex proteins have been shown to be important for many physiological and pathological processes, their role in kidney tissue has not been studied. In this study, we identified a mediator complex protein 22 (Med22) as a renal podocyte cell-enriched molecule. Podocyte-specific Med22 knockout mouse showed that Med22 was not needed for normal podocyte maturation. However, it was critical for the maintenance of podocyte health as the mice developed progressive glomerular disease and died due to renal failure. Detailed morphological analyses showed that Med22-deficiency in podocytes resulted in intracellular vacuole formation followed by podocyte loss. Moreover, Med22-deficiency in younger mice promoted the progression of glomerular disease, suggesting Med22-mediated processes may have a role in the development of glomerulopathies. This study shows for the first time that mediator complex has a critical role in kidney physiology. Nature Publishing Group UK 2020-11-18 /pmc/articles/PMC7676236/ /pubmed/33208756 http://dx.doi.org/10.1038/s41598-020-76870-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Rodriguez, Patricia Q.
Unnersjö-Jess, David
Zambrano, Sonia S.
Guo, Jing
Möller-Hackbarth, Katja
Blom, Hans
Jahnukainen, Timo
Ebarasi, Lwaki
Patrakka, Jaakko
Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
title Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
title_full Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
title_fullStr Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
title_full_unstemmed Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
title_short Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
title_sort inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676236/
https://www.ncbi.nlm.nih.gov/pubmed/33208756
http://dx.doi.org/10.1038/s41598-020-76870-0
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