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TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-β (TGF-β) is thought to be involved in the pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-β inhibitor sign...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627456/ https://www.ncbi.nlm.nih.gov/pubmed/37931000 http://dx.doi.org/10.1371/journal.pone.0293983 |
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author | Taga, Hideto Kishida, Tsunao Inoue, Yuta Yamamoto, Kenta Kotani, Shin-ichiro Masashi, Tsujimoto Ukimura, Osamu Mazda, Osam |
author_facet | Taga, Hideto Kishida, Tsunao Inoue, Yuta Yamamoto, Kenta Kotani, Shin-ichiro Masashi, Tsujimoto Ukimura, Osamu Mazda, Osam |
author_sort | Taga, Hideto |
collection | PubMed |
description | Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-β (TGF-β) is thought to be involved in the pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-β inhibitor significantly ameliorated IC/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC/PBS has not been comprehensively analyzed. TGF-β has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H₂O₂) and examined the effects of three TGF-β inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-β inhibitor treatment improved urinary function and histological changes in the IC/PBS mouse model, and SB431542 was most effective among the TGF-β inhibitors. In our present study, TGF-β inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-β inhibitor. |
format | Online Article Text |
id | pubmed-10627456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106274562023-11-07 TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients Taga, Hideto Kishida, Tsunao Inoue, Yuta Yamamoto, Kenta Kotani, Shin-ichiro Masashi, Tsujimoto Ukimura, Osamu Mazda, Osam PLoS One Research Article Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-β (TGF-β) is thought to be involved in the pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-β inhibitor significantly ameliorated IC/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC/PBS has not been comprehensively analyzed. TGF-β has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H₂O₂) and examined the effects of three TGF-β inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-β inhibitor treatment improved urinary function and histological changes in the IC/PBS mouse model, and SB431542 was most effective among the TGF-β inhibitors. In our present study, TGF-β inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-β inhibitor. Public Library of Science 2023-11-06 /pmc/articles/PMC10627456/ /pubmed/37931000 http://dx.doi.org/10.1371/journal.pone.0293983 Text en © 2023 Taga et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Taga, Hideto Kishida, Tsunao Inoue, Yuta Yamamoto, Kenta Kotani, Shin-ichiro Masashi, Tsujimoto Ukimura, Osamu Mazda, Osam TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients |
title | TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients |
title_full | TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients |
title_fullStr | TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients |
title_full_unstemmed | TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients |
title_short | TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients |
title_sort | tgf-β inhibitor treatment of h₂o₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627456/ https://www.ncbi.nlm.nih.gov/pubmed/37931000 http://dx.doi.org/10.1371/journal.pone.0293983 |
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