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10.3390/cells15040337
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Article

Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis

by
Sabrina Mota
1,
Austin Goodyke
2,
Elijah P. Ward
1,
Rani Mahyoob
1,
Yung-Chun Lee
3,
Sarah N. Bartolone
1,
Alyssa Mularski
1,
Michael B. Chancellor
1,4 and
Bernadette M. M. Zwaans
1,4,*
1
Department of Urology, Corewell Health William Beaumont University Hospital, Royal Oak, MI 48073, USA
2
Grand Rapids Research Center, Corewell Health, Grand Rapids, MI 49525, USA
3
Division of Biostatistics & Health Informatics, Corewell Health Research Institute, Royal Oak, MI 48073, USA
4
Department of Urology, William Beaumont School of Medicine, Oakland University, Rochester, MI 48309, USA
*
Author to whom correspondence should be addressed.
Cells 2026, 15(4), 337; https://doi.org/10.3390/cells15040337
Submission received: 7 January 2026 / Revised: 6 February 2026 / Accepted: 6 February 2026 / Published: 13 February 2026
(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)
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Abstract

Pelvic radiation therapy is an essential treatment for several pelvic malignancies, but it can lead to radiation cystitis (RC), a severe progressive inflammatory bladder disorder lacking effective diagnosis and therapeutic options. RC evolves through acute, latent, and chronic phases, ultimately resulting in bladder fibrosis, vascular damage, and hematuria. Here, we characterize the molecular and immunological features associated with RC progression using a preclinical mouse model. Building on a prior analysis of the acute and chronic phases, we examined the previously unanalyzed latent phase and integrated transcriptomics, immune cell profiling, inflammatory protein measurements, and bladder function assessments across all stages. Acute radiation injury was marked by the strong activation of apoptotic pathways, whereas latent and chronic phases were dominated by inflammatory signaling with distinct cytokine and chemokine signatures. The persistent upregulation of Cdkn1a (P21) was consistent with sustained senescence-associated signaling, while reductions in IL-27 and shifts in the granulocyte–lymphocyte-enriched immune population during the latent phase were consistent with altered immune regulatory states. At chronic stages, increased SASP-associated proteins and matrix remodeling mediators coincided with bladder functional decline. Together, these findings support a model in which radiation-induced senescence, coupled with immune dysregulation during the latent phase, are coordinated features accompanying inflammation, tissue remodeling, and bladder dysfunction in RC.
Keywords: radiation cystitis; cellular senescence; preclinical model; SASP radiation cystitis; cellular senescence; preclinical model; SASP

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MDPI and ACS Style

Mota, S.; Goodyke, A.; Ward, E.P.; Mahyoob, R.; Lee, Y.-C.; Bartolone, S.N.; Mularski, A.; Chancellor, M.B.; Zwaans, B.M.M. Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis. Cells 2026, 15, 337. https://doi.org/10.3390/cells15040337

AMA Style

Mota S, Goodyke A, Ward EP, Mahyoob R, Lee Y-C, Bartolone SN, Mularski A, Chancellor MB, Zwaans BMM. Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis. Cells. 2026; 15(4):337. https://doi.org/10.3390/cells15040337

Chicago/Turabian Style

Mota, Sabrina, Austin Goodyke, Elijah P. Ward, Rani Mahyoob, Yung-Chun Lee, Sarah N. Bartolone, Alyssa Mularski, Michael B. Chancellor, and Bernadette M. M. Zwaans. 2026. "Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis" Cells 15, no. 4: 337. https://doi.org/10.3390/cells15040337

APA Style

Mota, S., Goodyke, A., Ward, E. P., Mahyoob, R., Lee, Y.-C., Bartolone, S. N., Mularski, A., Chancellor, M. B., & Zwaans, B. M. M. (2026). Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis. Cells, 15(4), 337. https://doi.org/10.3390/cells15040337

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