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

Authors

• Sabrina Mota, Corewell Health East
• Austin Goodyke, Corewell Health West
• Elijah P. Ward, Corewell Health East
• Rani Mahyoob, Corewell Health East
• Yung-Chun Lee, Corewell Health West
• Sarah N. Bartolone, Corewell Health East
• Alyssa Mularski, Corewell Health East
• Michael B. Chancellor, Corewell Health East
• Bernadette M M Zwaans, Corewell Health East

Document Type

Article

Publication Date

2-2026

Publication Title

Cells

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.

Volume

15

Issue

4

First Page

337

Last Page

337

Recommended Citation

Mota, Sabrina; Goodyke, Austin; Ward, Elijah P.; Mahyoob, Rani; Lee, Yung-Chun; Bartolone, Sarah N.; Mularski, Alyssa; Chancellor, Michael B.; and Zwaans, Bernadette M M, "Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis." (2026). Articles. 370.
https://scholarlyworks.corewellhealth.org/urology_articles/370

Comments

Mota S, Goodyke A, Ward EP, Mahyoob R, Lee Y-C, Bartolone SN, et al. [Mularski A, Chancellor MB, Zwaans BMM]. Senescence-driven inflammation and immune dynamics in the progression of radiation cystitis. Cells. 2026;15(4):337. doi: 10.3390/cells15040337. PMID: 41744780.

DOI

10.3390/cells15040337

ISSN

2073-4409

PubMed ID

41744780