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Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats
BACKGROUND: There is a diurnal variation in the blood pressure fluctuation of hypertension, and blood pressure fluctuation abnormality is considered to be an independent risk factor for organ damage including cardiovascular complications. In the current study, we tried to identify molecules responsi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814221/ https://www.ncbi.nlm.nih.gov/pubmed/33463674 http://dx.doi.org/10.1093/ajh/hpaa123 |
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author | Murata, Yusuke Ueno, Takahiro Tanaka, Sho Kobayashi, Hiroki Okamura, Masahiro Hemmi, Seiichiro Fuke, Yoshinobu Matsumoto, Yoshiaki Abe, Masanori Fukuda, Noboru |
author_facet | Murata, Yusuke Ueno, Takahiro Tanaka, Sho Kobayashi, Hiroki Okamura, Masahiro Hemmi, Seiichiro Fuke, Yoshinobu Matsumoto, Yoshiaki Abe, Masanori Fukuda, Noboru |
author_sort | Murata, Yusuke |
collection | PubMed |
description | BACKGROUND: There is a diurnal variation in the blood pressure fluctuation of hypertension, and blood pressure fluctuation abnormality is considered to be an independent risk factor for organ damage including cardiovascular complications. In the current study, we tried to identify molecules responsible for blood pressure circadian rhythm formation under the control of the kidney biological clock in hypertension. METHODS: DNA microarray analysis was performed in kidneys from 5-week-old spontaneously hypertensive rats (SHRs)/Izm, stroke-prone SHR rats (SHRSP)/Izm, and Wistar Kyoto (WKY)/Izm rats. To detect variation, mouse tubular epithelial cells (TCMK-1) were stimulated with dexamethasone. We performed immunostaining and western blot analysis in the renal medulla of kidney from 5-week-old WKY rats and SHRs. RESULTS: We extracted 1,032 genes with E-box, a binding sequence for BMAL1 and CLOCK using a Gene Set Enrichment Analysis. In a microarray analysis, we identified 12 genes increased as more than 2-fold in the kidneys of SHRs and SHRSP in comparison to WKY rats. In a periodic regression analysis, phosphoribosyl pyrophosphate amidotransferase (Ppat) and fragile X mental retardation, autosomal homolog 1 (Fxr1) showed circadian rhythm. Immunocytochemistry revealed PPAT-positivity in nuclei and cytoplasm in the tubules, and FXR1-positivity in the cytoplasm of TCMK-1. In 5-week-old WKY rat and SHR kidneys, PPAT was localized in the nucleus and cytoplasm of the proximal and distal tubules, and FXR1 was localized to the cytoplasm of the proximal and distal tubules. CONCLUSIONS: PPAT and FXR1 are pivotal molecules in the control of blood pressure circadian rhythm by the kidney in hypertension. |
format | Online Article Text |
id | pubmed-7814221 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-78142212021-01-25 Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats Murata, Yusuke Ueno, Takahiro Tanaka, Sho Kobayashi, Hiroki Okamura, Masahiro Hemmi, Seiichiro Fuke, Yoshinobu Matsumoto, Yoshiaki Abe, Masanori Fukuda, Noboru Am J Hypertens Original Contributions BACKGROUND: There is a diurnal variation in the blood pressure fluctuation of hypertension, and blood pressure fluctuation abnormality is considered to be an independent risk factor for organ damage including cardiovascular complications. In the current study, we tried to identify molecules responsible for blood pressure circadian rhythm formation under the control of the kidney biological clock in hypertension. METHODS: DNA microarray analysis was performed in kidneys from 5-week-old spontaneously hypertensive rats (SHRs)/Izm, stroke-prone SHR rats (SHRSP)/Izm, and Wistar Kyoto (WKY)/Izm rats. To detect variation, mouse tubular epithelial cells (TCMK-1) were stimulated with dexamethasone. We performed immunostaining and western blot analysis in the renal medulla of kidney from 5-week-old WKY rats and SHRs. RESULTS: We extracted 1,032 genes with E-box, a binding sequence for BMAL1 and CLOCK using a Gene Set Enrichment Analysis. In a microarray analysis, we identified 12 genes increased as more than 2-fold in the kidneys of SHRs and SHRSP in comparison to WKY rats. In a periodic regression analysis, phosphoribosyl pyrophosphate amidotransferase (Ppat) and fragile X mental retardation, autosomal homolog 1 (Fxr1) showed circadian rhythm. Immunocytochemistry revealed PPAT-positivity in nuclei and cytoplasm in the tubules, and FXR1-positivity in the cytoplasm of TCMK-1. In 5-week-old WKY rat and SHR kidneys, PPAT was localized in the nucleus and cytoplasm of the proximal and distal tubules, and FXR1 was localized to the cytoplasm of the proximal and distal tubules. CONCLUSIONS: PPAT and FXR1 are pivotal molecules in the control of blood pressure circadian rhythm by the kidney in hypertension. Oxford University Press 2020-10-14 /pmc/articles/PMC7814221/ /pubmed/33463674 http://dx.doi.org/10.1093/ajh/hpaa123 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Contributions Murata, Yusuke Ueno, Takahiro Tanaka, Sho Kobayashi, Hiroki Okamura, Masahiro Hemmi, Seiichiro Fuke, Yoshinobu Matsumoto, Yoshiaki Abe, Masanori Fukuda, Noboru Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats |
title | Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats |
title_full | Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats |
title_fullStr | Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats |
title_full_unstemmed | Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats |
title_short | Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats |
title_sort | identification of clock genes related to hypertension in kidney from spontaneously hypertensive rats |
topic | Original Contributions |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814221/ https://www.ncbi.nlm.nih.gov/pubmed/33463674 http://dx.doi.org/10.1093/ajh/hpaa123 |
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