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Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension
Despite many readily available therapies, hypertensive kidney disease remains the second most prevalent cause of end-stage renal disease after diabetes, and continues to burden patient populations and escalate morbidity and mortality rates. Kinin B1 receptor (B1R) activation has been shown to have a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804098/ https://www.ncbi.nlm.nih.gov/pubmed/35118089 http://dx.doi.org/10.3389/fmed.2021.780834 |
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author | Basuli, Debargha Parekh, Rohan Umesh White, Acacia Thayyil, Abdullah Sriramula, Srinivas |
author_facet | Basuli, Debargha Parekh, Rohan Umesh White, Acacia Thayyil, Abdullah Sriramula, Srinivas |
author_sort | Basuli, Debargha |
collection | PubMed |
description | Despite many readily available therapies, hypertensive kidney disease remains the second most prevalent cause of end-stage renal disease after diabetes, and continues to burden patient populations and escalate morbidity and mortality rates. Kinin B1 receptor (B1R) activation has been shown to have a role in the development of hypertension, one of the major etiologies for chronic kidney disease. However, the role of B1R in hypertension induced renal injury and remodeling remains unexplored. Using a DOCA-salt-induced hypertensive mouse model, we investigated whether B1R deficiency reduces hypertensive renal injury and fibrosis. To further recognize the translational role of B1R, we examined the expression of B1R and its correlation with collagen deposition in renal biopsies from control and hypertensive kidney disease patients. Our data indicates that renal B1R expression was upregulated in the kidneys of DOCA-salt hypertensive mice. Genetic ablation of B1R protected the mice from DOCA-salt-induced renal injury and fibrosis by preventing inflammation and oxidative stress in the kidney. Cultured human proximal tubular epithelial cells expressed B1R and stimulation of B1R with an agonist resulted in increased oxidative stress. In human kidney biopsy samples, we found that the B1R immunoreactivity was not only significantly increased in hypertensive patients compared to normotensive patients, but also there is a positive correlation between B1R expression and renal fibrosis levels. Taken together, our results identify a critical role of B1R in the development of inflammation and fibrosis of the kidney in hypertension. |
format | Online Article Text |
id | pubmed-8804098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88040982022-02-02 Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension Basuli, Debargha Parekh, Rohan Umesh White, Acacia Thayyil, Abdullah Sriramula, Srinivas Front Med (Lausanne) Medicine Despite many readily available therapies, hypertensive kidney disease remains the second most prevalent cause of end-stage renal disease after diabetes, and continues to burden patient populations and escalate morbidity and mortality rates. Kinin B1 receptor (B1R) activation has been shown to have a role in the development of hypertension, one of the major etiologies for chronic kidney disease. However, the role of B1R in hypertension induced renal injury and remodeling remains unexplored. Using a DOCA-salt-induced hypertensive mouse model, we investigated whether B1R deficiency reduces hypertensive renal injury and fibrosis. To further recognize the translational role of B1R, we examined the expression of B1R and its correlation with collagen deposition in renal biopsies from control and hypertensive kidney disease patients. Our data indicates that renal B1R expression was upregulated in the kidneys of DOCA-salt hypertensive mice. Genetic ablation of B1R protected the mice from DOCA-salt-induced renal injury and fibrosis by preventing inflammation and oxidative stress in the kidney. Cultured human proximal tubular epithelial cells expressed B1R and stimulation of B1R with an agonist resulted in increased oxidative stress. In human kidney biopsy samples, we found that the B1R immunoreactivity was not only significantly increased in hypertensive patients compared to normotensive patients, but also there is a positive correlation between B1R expression and renal fibrosis levels. Taken together, our results identify a critical role of B1R in the development of inflammation and fibrosis of the kidney in hypertension. Frontiers Media S.A. 2022-01-18 /pmc/articles/PMC8804098/ /pubmed/35118089 http://dx.doi.org/10.3389/fmed.2021.780834 Text en Copyright © 2022 Basuli, Parekh, White, Thayyil and Sriramula. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Basuli, Debargha Parekh, Rohan Umesh White, Acacia Thayyil, Abdullah Sriramula, Srinivas Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension |
title | Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension |
title_full | Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension |
title_fullStr | Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension |
title_full_unstemmed | Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension |
title_short | Kinin B1 Receptor Mediates Renal Injury and Remodeling in Hypertension |
title_sort | kinin b1 receptor mediates renal injury and remodeling in hypertension |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804098/ https://www.ncbi.nlm.nih.gov/pubmed/35118089 http://dx.doi.org/10.3389/fmed.2021.780834 |
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