Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 9 (1), 19169

Dysregulation of Bladder Corticotropin-Releasing Hormone Receptor in the Pathogenesis of Human Interstitial Cystitis/Bladder Pain Syndrome

Affiliations

Dysregulation of Bladder Corticotropin-Releasing Hormone Receptor in the Pathogenesis of Human Interstitial Cystitis/Bladder Pain Syndrome

Jia-Fong Jhang et al. Sci Rep.

Abstract

Stress is associated with exacerbated symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). To investigate the mechanism of stress implicated on IC/BPS, we investigated expression of stress-response receptor corticotropin-releasing hormone receptor (CRHR) in bladder from IC/BPS patients. Twenty-three IC/BPS patients with Hunner's lesion (HIC), 51 IC/BPS patients without Hunner's lesion (NHIC), and 24 patients with stress urinary incontinence as controls were enrolled. Cystoscopic biopsies of bladder wall including mucosa and submucosa were obtained from all patients. Western blotting was used to investigate the bladder expression of the CRHR1 and CRHR2. Immunochemical staining revealed CRHR1 expression was mainly located in the submucosa while CRHR2 expression was mainly in uroepithelial cells. Compared to control subjects, the CRHR1 expression was significantly higher, while CRHR2 expression was significantly lower in IC/BPS patients. Further analysis of patients with HIC, NHIC, and control subjects showed that bladder in patients with HIC had significantly higher expressions of CRHR1 and significantly lower CRHR2. CRHR2 expression was significantly negatively correlated with O'Leary-Sant score and bladder pain. Our results indicate dysregulation of bladder CRHR1 and CRHR2 in patients with IC/BPS, and suggest CRH signaling may be associated with IC/BPS symptoms.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The representative western blotting figures of the bladder targets. The bands were cut from patients with HIC, NHIC and control subjects (from different experiments). CRHR1, CRHR2, NGF, E-cadherin were detected in bladder biopsy specimens, whereas UCN1 and UCN2 were not clearly expressed. Their corresponding full-length blots are presented in Supplementary Figs. 1–4.
Figure 2
Figure 2
The immunofluorescence staining of CRHR1 and CRHR2 in the bladder of control, NHIC, and NHIC patients. The immunochemical staining revealed expression of CRHR1 in bladder submucosa but not in uroepithelial cells (white arrow). In contrast, CRHR2 expression was found mainly in uroepithelial cells (white arrow).
Figure 3
Figure 3
The double immunochemical staining of CRHR1 and tryptase in the bladder of IC/BPS patients. (A) CRHR1; (B) typtase; (C) merge figure for CRHR1, tryptase and DAPI. It showed the co-expression of CRHR1 and tryptase in the IC/BPS lamina propria (white arrow).
Figure 4
Figure 4
The total IC/BPS patients and control subjects bladder western blot results for CRHR1, CRHR2, NGF and E-cadherine. Statistical significance was tested with independent-T test. *p < 0.05.
Figure 5
Figure 5
The HIC, NHIC and control subjects bladder western blot results for CRHR1, CRHR2, NGF and E-cadherine. Statistical significance was tested with one-way ANOVA followed by Scheffe posthoc test. *p < 0.05.

Similar articles

See all similar articles

References

    1. Hanno PM, Erickson D, Moldwin R, Faraday MM. American Urological Association Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193:1545–1553. doi: 10.1016/j.juro.2015.01.086. - DOI - PubMed
    1. Hauser PJ, et al. Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis. J Urol. 2015;194:571–577. doi: 10.1016/j.juro.2015.01.090. - DOI - PMC - PubMed
    1. Jhang JF, Hsu YH, Kuo HC. Urothelial Functional Protein and Sensory Receptors in Patients With Interstitial Cystitis/Bladder Pain Syndrome With and Without Hunner’s Lesion. Urology. 2016;98:44–49. doi: 10.1016/j.urology.2016.08.029. - DOI - PubMed
    1. Sun Y, Keay S, Lehrfeld TJ, Chai TC. Changes in adenosine triphosphate-stimulated ATP release suggest association between cytokine and purinergic signaling in bladder urothelial cells. Urology. 2009;74:1163–1168. doi: 10.1016/j.urology.2009.02.066. - DOI - PMC - PubMed
    1. Birder LA, et al. Beyond neurons: Involvement of urothelial and glial cells in bladder function. Neurourol Urodyn. 2010;29:88–96. doi: 10.1002/nau.20747. - DOI - PMC - PubMed
Feedback