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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0293983&type=printable |
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| author | Hideto Taga Tsunao Kishida Yuta Inoue Kenta Yamamoto Shin-Ichiro Kotani Tsujimoto Masashi Osamu Ukimura Osam Mazda |
| author_facet | Hideto Taga Tsunao Kishida Yuta Inoue Kenta Yamamoto Shin-Ichiro Kotani Tsujimoto Masashi Osamu Ukimura Osam Mazda |
| author_sort | Hideto Taga |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T00:20:34Z |
| format | Article |
| id | doaj.art-96e66406579e414f8d90c481f14aeccd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-09T00:20:34Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-96e66406579e414f8d90c481f14aeccd2023-12-12T05:35:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011811e029398310.1371/journal.pone.0293983TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients.Hideto TagaTsunao KishidaYuta InoueKenta YamamotoShin-Ichiro KotaniTsujimoto MasashiOsamu UkimuraOsam MazdaInterstitial 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0293983&type=printable |
| spellingShingle | Hideto Taga Tsunao Kishida Yuta Inoue Kenta Yamamoto Shin-Ichiro Kotani Tsujimoto Masashi Osamu Ukimura Osam Mazda TGF-β inhibitor treatment of H₂O₂-induced cystitis models provides biochemical mechanism for elucidating interstitial cystitis/painful bladder syndrome patients. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0293983&type=printable |
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