Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder
Abstract The underlying mechanism of radiation cystitis remains unknown, however, angiogenesis induced by hypoxia seems to be important because hyperbaric oxygen therapy which suppresses HIF-1 is clinically effective and significantly associated with androgen receptor signaling. We herein assessed t...
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-15245-9 |
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| author | Takahiro Komori Hiroki Ide Junichi Fukada Yuto Baba Kazuhiro Matsumoto Hiroshi Miyamoto Mototsugu Oya |
| author_facet | Takahiro Komori Hiroki Ide Junichi Fukada Yuto Baba Kazuhiro Matsumoto Hiroshi Miyamoto Mototsugu Oya |
| author_sort | Takahiro Komori |
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| description | Abstract The underlying mechanism of radiation cystitis remains unknown, however, angiogenesis induced by hypoxia seems to be important because hyperbaric oxygen therapy which suppresses HIF-1 is clinically effective and significantly associated with androgen receptor signaling. We herein assessed the impact of androgen deprivation therapy on radiotherapy-induced bladder hemorrhage in men with prostate cancer and that of androgen receptor signaling on angiogenesis in irradiated bladder cell lines and a mouse model of radiation cystitis. In 507 patients with prostate cancer undergoing external beam radiation therapy, univariate (hazard ratio 0.61, p = 0.039) and multivariate (hazard ratio 0.50, p = 0.006) analyses revealed that the use of androgen deprivation therapy was associated with a significantly lower risk of gross hematuria. In irradiated bladder cells, the levels of FLT1 and KDR expression were significantly elevated when pretreated with dihydrotestosterone, which was abolished by an anti-androgen hydroxyflutamide. In male mice with radiation cystitis, castration significantly reduced the incidence of hematuria. Correspondingly, microvessel density and VEGFR expression in the bladders in the castration group were significantly lower than those in the sham surgery group. Our results suggest that androgen receptor activation contributes to inducing angiogenesis in irradiated bladder cells. Androgen deprivation therapy thus has a potential for preventing radiation cystitis. |
| format | Article |
| id | doaj-art-e1db42fb99c74cd5b6f8b55ee9e04816 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-e1db42fb99c74cd5b6f8b55ee9e048162025-08-20T03:45:53ZengNature PortfolioScientific Reports2045-23222025-08-0115111110.1038/s41598-025-15245-9Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladderTakahiro Komori0Hiroki Ide1Junichi Fukada2Yuto Baba3Kazuhiro Matsumoto4Hiroshi Miyamoto5Mototsugu Oya6Department of Urology, Keio University School of MedicineDepartment of Urology, Keio University School of MedicineDepartment of Radiology, Keio University School of MedicineDepartment of Urology, Keio University School of MedicineDepartment of Urology, Keio University School of MedicineDepartments of Pathology and Laboratory Medicine and Urology, University of Rochester Medical CenterDepartment of Urology, Keio University School of MedicineAbstract The underlying mechanism of radiation cystitis remains unknown, however, angiogenesis induced by hypoxia seems to be important because hyperbaric oxygen therapy which suppresses HIF-1 is clinically effective and significantly associated with androgen receptor signaling. We herein assessed the impact of androgen deprivation therapy on radiotherapy-induced bladder hemorrhage in men with prostate cancer and that of androgen receptor signaling on angiogenesis in irradiated bladder cell lines and a mouse model of radiation cystitis. In 507 patients with prostate cancer undergoing external beam radiation therapy, univariate (hazard ratio 0.61, p = 0.039) and multivariate (hazard ratio 0.50, p = 0.006) analyses revealed that the use of androgen deprivation therapy was associated with a significantly lower risk of gross hematuria. In irradiated bladder cells, the levels of FLT1 and KDR expression were significantly elevated when pretreated with dihydrotestosterone, which was abolished by an anti-androgen hydroxyflutamide. In male mice with radiation cystitis, castration significantly reduced the incidence of hematuria. Correspondingly, microvessel density and VEGFR expression in the bladders in the castration group were significantly lower than those in the sham surgery group. Our results suggest that androgen receptor activation contributes to inducing angiogenesis in irradiated bladder cells. Androgen deprivation therapy thus has a potential for preventing radiation cystitis.https://doi.org/10.1038/s41598-025-15245-9Androgen receptorAngiogenesisProstate cancerRadiation cystitis and radiotherapy |
| spellingShingle | Takahiro Komori Hiroki Ide Junichi Fukada Yuto Baba Kazuhiro Matsumoto Hiroshi Miyamoto Mototsugu Oya Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder Scientific Reports Androgen receptor Angiogenesis Prostate cancer Radiation cystitis and radiotherapy |
| title | Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder |
| title_full | Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder |
| title_fullStr | Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder |
| title_full_unstemmed | Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder |
| title_short | Androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder |
| title_sort | androgen receptor signaling induces hemorrhage and angiogenesis in the irradiated bladder |
| topic | Androgen receptor Angiogenesis Prostate cancer Radiation cystitis and radiotherapy |
| url | https://doi.org/10.1038/s41598-025-15245-9 |
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