Journal article
Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications
The Journal of urology, Vol.207(3), pp.635-646
03/2022
DOI: 10.1097/JU.0000000000002278
PMID: 34694138
Abstract
The aim of our study was to elucidate biological changes in Hunner lesions, which underlie the pathophysiology of Hunner-type interstitial cystitis, by characterizing their whole transcriptome and immunopathological profiles.
Paired bladder mucosal biopsies, 1 sample each from the Hunner lesion and nonlesion area, were obtained from 25 patients with Hunner-type interstitial cystitis. The samples were subjected to whole-transcriptome profiling; immunohistochemical quantification of CD3, CD4, CD8, CD20, CD138, mast cell tryptase, cytokeratin and HIF1α; and quantitative polymerase chain reaction for
and
. The results were compared between the lesion and nonlesion areas.
RNA sequencing identified 109 differentially expressed genes and 30 significantly enriched biological pathways in Hunner lesions. Up-regulated pathways (24) included HIF1α signaling pathway, PI3K-Akt signaling pathway, RAS signaling pathway and MAPK signaling pathway. By contrast, down-regulated pathways (6) included basal cell carcinoma and protein digestion and absorption. The mRNA levels of
,
and
, and the HIF1α protein level were significantly higher in lesion areas. Otherwise, there were no significant differences between the lesion and nonlesion samples in terms of mRNA levels of inflammatory cytokines or histological features such as lymphoplasmacytic and mast cell infiltration, epithelial denudation and CD4/CD8 T-lymphocyte ratio.
Our findings demonstrate significant overexpression of HIF1α and up-regulation of its related biological pathways in Hunner lesions. The results indicate that ischemia, in conjunction with inflammation, plays a pathophysiological role in this subtype of interstitial cystitis/bladder pain syndrome, particularly in Hunner lesions.
Details
- Title: Subtitle
- Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications
- Creators
- Yoshiyuki Akiyama - The University of TokyoJimpei Miyakawa - The University of TokyoMichael A O'Donnell - University of IowaKarl J Kreder - University of IowaYi Luo - University of IowaDaichi Maeda - Kanazawa UniversityTetsuo Ushiku - The University of TokyoHaruki Kume - The University of TokyoYukio Homma - Japanese Red Cross Medical Center
- Resource Type
- Journal article
- Publication Details
- The Journal of urology, Vol.207(3), pp.635-646
- DOI
- 10.1097/JU.0000000000002278
- PMID
- 34694138
- ISSN
- 0022-5347
- eISSN
- 1527-3792
- Language
- English
- Date published
- 03/2022
- Academic Unit
- Obstetrics and Gynecology; Urology
- Record Identifier
- 9984319983402771
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