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Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice
The kidney’s inherent complexity has made identifying cell-specific pathways challenging, particularly when temporally associating them with the dynamic pathophysiology of acute kidney injury (AKI). Here, we combine renal cell-specific luciferase reporter mice using a chemoselective luciferin to gui...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718519/ https://www.ncbi.nlm.nih.gov/pubmed/31508501 http://dx.doi.org/10.1038/s42003-019-0571-7 |
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author | Miyazaki, Tomoaki Gharib, Sina A. Hsu, Yun-Wei A. Xu, Katherine Khodakivskyi, Pavlo Kobayashi, Akio Paragas, Jason Klose, Alexander D. Francis, Kevin P. Dubikovskaya, Elena Page-McCaw, Patrick S. Barasch, Jonathan Paragas, Neal |
author_facet | Miyazaki, Tomoaki Gharib, Sina A. Hsu, Yun-Wei A. Xu, Katherine Khodakivskyi, Pavlo Kobayashi, Akio Paragas, Jason Klose, Alexander D. Francis, Kevin P. Dubikovskaya, Elena Page-McCaw, Patrick S. Barasch, Jonathan Paragas, Neal |
author_sort | Miyazaki, Tomoaki |
collection | PubMed |
description | The kidney’s inherent complexity has made identifying cell-specific pathways challenging, particularly when temporally associating them with the dynamic pathophysiology of acute kidney injury (AKI). Here, we combine renal cell-specific luciferase reporter mice using a chemoselective luciferin to guide the acquisition of cell-specific transcriptional changes in C57BL/6 background mice. Hydrogen peroxide generation, a common mechanism of tissue damage, was tracked using a peroxy-caged-luciferin to identify optimum time points for immunoprecipitation of labeled ribosomes for RNA-sequencing. Together, these tools revealed a profound impact of AKI on mitochondrial pathways in the collecting duct. In fact, targeting the mitochondria with an antioxidant, ameliorated not only hydrogen peroxide generation, but also significantly reduced oxidative stress and the expression of the AKI biomarker, LCN2. This integrative approach of coupling physiological imaging with transcriptomics and drug testing revealed how the collecting duct responds to AKI and opens new venues for cell-specific predictive monitoring and treatment. |
format | Online Article Text |
id | pubmed-6718519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67185192019-09-10 Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice Miyazaki, Tomoaki Gharib, Sina A. Hsu, Yun-Wei A. Xu, Katherine Khodakivskyi, Pavlo Kobayashi, Akio Paragas, Jason Klose, Alexander D. Francis, Kevin P. Dubikovskaya, Elena Page-McCaw, Patrick S. Barasch, Jonathan Paragas, Neal Commun Biol Article The kidney’s inherent complexity has made identifying cell-specific pathways challenging, particularly when temporally associating them with the dynamic pathophysiology of acute kidney injury (AKI). Here, we combine renal cell-specific luciferase reporter mice using a chemoselective luciferin to guide the acquisition of cell-specific transcriptional changes in C57BL/6 background mice. Hydrogen peroxide generation, a common mechanism of tissue damage, was tracked using a peroxy-caged-luciferin to identify optimum time points for immunoprecipitation of labeled ribosomes for RNA-sequencing. Together, these tools revealed a profound impact of AKI on mitochondrial pathways in the collecting duct. In fact, targeting the mitochondria with an antioxidant, ameliorated not only hydrogen peroxide generation, but also significantly reduced oxidative stress and the expression of the AKI biomarker, LCN2. This integrative approach of coupling physiological imaging with transcriptomics and drug testing revealed how the collecting duct responds to AKI and opens new venues for cell-specific predictive monitoring and treatment. Nature Publishing Group UK 2019-09-02 /pmc/articles/PMC6718519/ /pubmed/31508501 http://dx.doi.org/10.1038/s42003-019-0571-7 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Miyazaki, Tomoaki Gharib, Sina A. Hsu, Yun-Wei A. Xu, Katherine Khodakivskyi, Pavlo Kobayashi, Akio Paragas, Jason Klose, Alexander D. Francis, Kevin P. Dubikovskaya, Elena Page-McCaw, Patrick S. Barasch, Jonathan Paragas, Neal Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice |
title | Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice |
title_full | Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice |
title_fullStr | Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice |
title_full_unstemmed | Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice |
title_short | Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice |
title_sort | cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718519/ https://www.ncbi.nlm.nih.gov/pubmed/31508501 http://dx.doi.org/10.1038/s42003-019-0571-7 |
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