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Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice

dc.contributor.authorPage-McCaw, Patrick S.
dc.identifier.citationMiyazaki, T., Gharib, S. A., Hsu, Y. A., Xu, K., Khodakivskyi, P., Kobayashi, A., Paragas, J., Klose, A. D., Francis, K. P., Dubikovskaya, E., Page-McCaw, P. S., Barasch, J., & Paragas, N. (2019). Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice. Communications biology, 2, 326.
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at
dc.description.abstractThe 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.en_US
dc.description.sponsorshipThis work was supported by a kind gift from Bill and June Boeing and the Aldara Foundation, startup funding from the University of Washington School of Medicine and Division of Nephrology, the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant DK094873 and pilot awards DK017047 and DK89507.en_US
dc.publisherCommunications Biologyen_US
dc.rightsOpen 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
dc.titleCell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in miceen_US

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