Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. Analysis of inflammatory proteins, or cytokines in the urine or serum provides another diagnostic foundation forIC/BPS subtypes. The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. This article reviews recent research on the pathomechanisms of IC, which might help us in mapping the heterogeneity of the disease.
Adhesives ; Apoptosis ; Autoimmunity ; Biomarkers ; Cadherins ; Chondroitin Sulfates ; Cystitis ; Cytokines ; Epithelium ; Gene Expression ; Homeostasis ; Inflammation ; Lower Urinary Tract Symptoms ; Mast Cells ; Neurogenic Inflammation ; Nocturia ; Phenotype ; Population Characteristics* ; Tight Junctions ; Urinary Bladder ; Urinary Bladder Diseases ; Urinary Tract Infections ; Uroplakins

Purpose: To investigate urothelial cell proliferation, cytoskeleton, inflammation, and barrier function protein expressions in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) after intravesical platelet-rich plasma (PRP) injections Methods: A total of 19 patients with IC/BPS underwent 4 monthly intravesical PRP injections. Bladder biopsies were taken at the first and fourth PRP treatment. The bladder specimens were analyzed using the Western blot and immunochemical staining for progenitor cell markers for sonic hedgehog (Shh), CD34, and cytoskeleton proteins cytokeratin 5 (CK5), CK14, CK20; barrier function markers for zonula occludens-1 (ZO-1), E-cadherin, and intercellular adhesive molecule-1, tryptase and transforming growth factor-β (TGF-β). Global response assessment (GRA) was used to evaluate treatment outcomes. Results: The mean age of patients was 55.6 years. After PRP injections, the functional bladder capacity and maximum flow rate increased, and the visual analogue scale (VAS) of pain, interstitial cystitis (IC) symptom index, IC problem index, O’Leary-Sant symptom score, and GRA improved in all patients. Urothelium Shh, CK5, ZO-1, E-cadherin, and TGF-β expressions increased significantly after repeated PRP injections. By subgrouping, according to PRP treatment outcomes, significant increases in Shh, E-cadherin, and ZO-1 expressions were noted only in patients with GRA ≥1 or improved VAS, but not in patients with GRA=0 and no improvement in VAS. Conclusions The level of urothelial barrier function protein and cell proliferation protein expression in the patients with IC/BPS was increased after repeat intravesical PRP injections. Intravesical repeat PRP injections may have potential to improve urothelial health and result in symptoms improvement in the patients with IC/BPS.