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Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat
We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with normal rats (control group; n = 10). We measured th...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966957/ https://www.ncbi.nlm.nih.gov/pubmed/36835398 http://dx.doi.org/10.3390/ijms24043982 |
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author | Akaihata, Hidenori Matsuoka, Kanako Hata, Junya Harigane, Yuki Yaginuma, Kei Endo, Yu Imai, Hitomi Matsuoka, Yuta Onagi, Akifumi Tanji, Ryo Honda-Takinami, Ruriko Hoshi, Seiji Koguchi, Tomoyuki Sato, Yuichi Kataoka, Masao Uemura, Motohide Igawa, Yasuhiko Kojima, Yoshiyuki |
author_facet | Akaihata, Hidenori Matsuoka, Kanako Hata, Junya Harigane, Yuki Yaginuma, Kei Endo, Yu Imai, Hitomi Matsuoka, Yuta Onagi, Akifumi Tanji, Ryo Honda-Takinami, Ruriko Hoshi, Seiji Koguchi, Tomoyuki Sato, Yuichi Kataoka, Masao Uemura, Motohide Igawa, Yasuhiko Kojima, Yoshiyuki |
author_sort | Akaihata, Hidenori |
collection | PubMed |
description | We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with normal rats (control group; n = 10). We measured the expression of mast cell tryptase (MCT) and protease-activated receptor 2 (PAR2), which are correlated with C fiber activation via MCT, and Uroplakins (UP Ia, Ib, II and III), which are critical to urothelial barrier function, via Western blotting. The effects of FSLLRY-NH2, a PAR2 antagonist, administered intravenously, on the bladder function of CBI rats were evaluated with a cystometrogram. In the CBI group, the MC number in the bladder was significantly greater (p = 0.03), and the expression of MCT (p = 0.02) and PAR2 (p = 0.02) was significantly increased compared to that of the control group. The 10 μg/kg FSLLRY-NH2 injection significantly increased the micturition interval of CBI rats (p = 0.03). The percentage of UP-II-positive cells on the urothelium with immunohistochemical staining was significantly lower in the CBI group than in the control group (p < 0.01). Chronic ischemia induces urothelial barrier dysfunction via impairing UP II, consequently inducing MC infiltration into the bladder wall and increased PAR2 expression. PAR2 activation by MCT may contribute to bladder hyperactivity. |
format | Online Article Text |
id | pubmed-9966957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99669572023-02-26 Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat Akaihata, Hidenori Matsuoka, Kanako Hata, Junya Harigane, Yuki Yaginuma, Kei Endo, Yu Imai, Hitomi Matsuoka, Yuta Onagi, Akifumi Tanji, Ryo Honda-Takinami, Ruriko Hoshi, Seiji Koguchi, Tomoyuki Sato, Yuichi Kataoka, Masao Uemura, Motohide Igawa, Yasuhiko Kojima, Yoshiyuki Int J Mol Sci Article We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with normal rats (control group; n = 10). We measured the expression of mast cell tryptase (MCT) and protease-activated receptor 2 (PAR2), which are correlated with C fiber activation via MCT, and Uroplakins (UP Ia, Ib, II and III), which are critical to urothelial barrier function, via Western blotting. The effects of FSLLRY-NH2, a PAR2 antagonist, administered intravenously, on the bladder function of CBI rats were evaluated with a cystometrogram. In the CBI group, the MC number in the bladder was significantly greater (p = 0.03), and the expression of MCT (p = 0.02) and PAR2 (p = 0.02) was significantly increased compared to that of the control group. The 10 μg/kg FSLLRY-NH2 injection significantly increased the micturition interval of CBI rats (p = 0.03). The percentage of UP-II-positive cells on the urothelium with immunohistochemical staining was significantly lower in the CBI group than in the control group (p < 0.01). Chronic ischemia induces urothelial barrier dysfunction via impairing UP II, consequently inducing MC infiltration into the bladder wall and increased PAR2 expression. PAR2 activation by MCT may contribute to bladder hyperactivity. MDPI 2023-02-16 /pmc/articles/PMC9966957/ /pubmed/36835398 http://dx.doi.org/10.3390/ijms24043982 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Akaihata, Hidenori Matsuoka, Kanako Hata, Junya Harigane, Yuki Yaginuma, Kei Endo, Yu Imai, Hitomi Matsuoka, Yuta Onagi, Akifumi Tanji, Ryo Honda-Takinami, Ruriko Hoshi, Seiji Koguchi, Tomoyuki Sato, Yuichi Kataoka, Masao Uemura, Motohide Igawa, Yasuhiko Kojima, Yoshiyuki Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat |
title | Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat |
title_full | Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat |
title_fullStr | Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat |
title_full_unstemmed | Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat |
title_short | Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2—Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat |
title_sort | involvement of mast-cell-tryptase- and protease-activated receptor 2—mediated signaling and urothelial barrier dysfunction with reduced uroplakin ii expression in bladder hyperactivity induced by chronic bladder ischemia in the rat |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966957/ https://www.ncbi.nlm.nih.gov/pubmed/36835398 http://dx.doi.org/10.3390/ijms24043982 |
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