江景翔、張嘉峰、郭漢崇

佛教慈濟醫療財團法人花蓮慈濟醫院 泌尿部

Ching-Hsiang Chiang, Jia-Fong Jhang, Hann-Chorng Kuo

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan

 

Purpose: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is related to urothelial dysfunction and chronic inflammation. This study tried to investigate the inflammation expression, the barrier dysfunction and the protein expression related to regeneration in the IC/BPS urothelium of different phenotypes.

Materials and Methods: We enrolled 85 patients suffered from IC/BPS who were admitted to our hospital for treatment and 22 stress urinary incontinence with stable bladder as normal control were enrolled. The IC/BPS groups was divided into four categories according to severity of cystoscopy picture: non-ulcer grade I, II, III (n=64) or ulcer-type IC (n=21). The endoscopic cold-cup was performed to take bladder specimens, investigated by Western blotting with quantification and qualitative immunofluorescence staining (IHC) for protein E-cadherin (E-cad), cytokeratin 5 (CK5), CK14, CK20, and cell proliferation protein as sonic hedgehog (SHH), tumor protein 63 (TP63), fibroblast growth factor receptors 3 (FGFR3), FGFR4 and BCL2-associated X protein (BAX). GAPDH was used as normalizing protein for the quantification.

Results: In the part of urothelial cytoskeleton protein and cell adhesion molecule, the E-cadherin, CK14 and CK20 expression were decreased in the Hunner’s ulcer-type IC patients. However, the CK5 expression was higher in the HIC patients (Fig. 1A). Among the non-ulcer type IC patient, the CK20 expression was lower, but the CK5 expression was higher in grade 3 glomerulation (Fig. 1B). As for cell proliferation and apoptotic proteins, the SHH, P63, FGFR3 and FGFR4 expression were lower in the patient with HIC and the BAX expression was higher in the HIC patients (Fig. 1C). Patient with grade III glomerulation hemorrhage got lower urothelial P63 and FGFR4 expression, while the BAX expression was higher than Gr.I to II non ulcer type IC patient (Fig. 1D). In IHC staining result, the expression of E-cadherin was decreased in the NHIC and HIC patients (Fig. 2A). The CK5 expression was mainly located in basal layer in control group bladder but not limited in basal layer of HIC bladder. CK14 expression only could be found in basal cells of the HIC bladder rather than entire layer like control group. CK20 expression could not be detected in HIC bladder (Fig. 2A). SHH, P63, FGFR3 and FGFR4 expression were decreased in the HIC bladder (Fig. 2B).

Conclusions: The decreased urothelial cytoskeleton and cell proliferation protein expression suggest intersitial cystitis/bladder pain syndrome patients with Hunner’s lesion and grade 3 glomerulation might be different from the other type patients.