Molecular characterization of chronic inflammatory diseases of the urinary bladder based on next-generation RNA sequencing and digital image analysis

Yoshiyuki Akiyama; Jimpei Miyakawa; Masafumi Horie; Tetsuichi Saito; Tomonori Minagawa; Tetsuo Ushiku; Akiteru Goto; Haruki Kume; Yukio Homma; Yi Luo; Daichi Maeda

doi:10.1038/s41598-025-22053-8

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Molecular characterization of chronic inflammatory diseases of the urinary bladder based on next-generation RNA sequencing and digital image analysis

Journal article

Open access

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Molecular characterization of chronic inflammatory diseases of the urinary bladder based on next-generation RNA sequencing and digital image analysis

Yoshiyuki Akiyama, Jimpei Miyakawa, Masafumi Horie, Tetsuichi Saito, Tomonori Minagawa, Tetsuo Ushiku, Akiteru Goto, Haruki Kume, Yukio Homma, Yi Luo, …

Scientific reports, Vol.15(1), 38169

10/31/2025

DOI: 10.1038/s41598-025-22053-8

PMCID: PMC12578850

PMID: 41174026

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Abstract

This study aimed to elucidate distinct cellular and immunological characteristics associated with chronic inflammatory conditions of the urinary bladder, including Hunner-type interstitial cystitis (HIC), bacillus Calmette-Guérin (BCG)-related cystitis, follicular cystitis (FC), and chronic bacterial cystitis (CBC). Transcriptomic analyses using next-generation RNA sequencing, along with quantitative polymerase chain reaction, were performed on mucosal bladder biopsies to assess the whole transcriptional and immune-response profiles. Furthermore, digital immunohistochemical quantification evaluated urothelial denudation and the densities of infiltrating immune cells, including T-lymphocytes, B-lymphocytes, mast cells, and plasma cells. HIC specimens exhibited a markedly distinct transcriptional profile, with 3,566 differentially expressed genes and enrichment of 116 biological processes particularly associated with microbial response and heightened autoimmunity with Th1/Th17 axis polarization. Histologically, HIC bladders demonstrated significant epithelial denudation, elevated IL-17-positive cell density, and increased plasma cell ratios compared to other cystitis types. No significant differences were observed in overall lymphoplasmacytic or mast cell densities, nor in B cell ratios among the groups. These findings underscore a unique immunopathological signature in HIC, characterized by plasma cell predominance within a Th1/17-polarized immune environment and epithelial denudation, offering new insights into its pathogenesis and therapeutic targeting.

Adult

Aged

Chronic Disease

Cystitis - genetics

Cystitis - pathology

Cystitis, Interstitial - genetics

Cystitis, Interstitial - immunology

Cystitis, Interstitial - pathology

Female

Gene Expression Profiling

High-Throughput Nucleotide Sequencing

Humans

Inflammation - genetics

Inflammation - pathology

Male

Mast Cells

Middle Aged

Sequence Analysis, RNA

Transcriptome

Urinary Bladder - immunology

Urinary Bladder - metabolism

Urinary Bladder - pathology

Details

Title: Subtitle: Molecular characterization of chronic inflammatory diseases of the urinary bladder based on next-generation RNA sequencing and digital image analysis
Creators: Yoshiyuki Akiyama - Shinshu University
Jimpei Miyakawa - The University of Tokyo
Masafumi Horie - Kobe University
Tetsuichi Saito - Shinshu University
Tomonori Minagawa - Shinshu University
Tetsuo Ushiku - The University of Tokyo
Akiteru Goto - Akita University
Haruki Kume - The University of Tokyo
Yukio Homma - Kyorin University
Yi Luo - University of Iowa
Daichi Maeda - Garvan Institute of Medical Research
Resource Type: Journal article
Publication Details: Scientific reports, Vol.15(1), 38169
DOI: 10.1038/s41598-025-22053-8
PMID: 41174026
PMCID: PMC12578850
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: Springer Nature
Grant note: 22K16788 / Japan Society for the Promotion of Science 24ek0109763 / Japan Agency for Medical Research and Development 25K02771 / Japan Society for the Promotion of Science,Japan 24FC1017 / Ministry of Health, Labour and Welfare
Language: English
Date published: 10/31/2025
Academic Unit: Urology
Record Identifier: 9985024146702771

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