Improved Urothelial Cell Proliferation, Cytoskeleton and Barrier Function Protein Expression in the Patients With Interstitial Cystitis/Bladder Pain Syndrome After Intravesical Platelet-Rich Plasma Injection
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
Abstract
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.
참고문헌 (21)
- Keay S, "Cell signaling in interstitial cystitis", painful bladder syndrome, 2008, pp.20, 2174~2179
- Shie JH, "Higher levels of cell apoptosis and abnormal Ecadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis", painful bladder syndrome, 2011, pp.108(2 Pt 2), E136~E141
- Shie JH, "Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis", painful bladder syndrome, 2012, pp.79, 484.e7~484.e13
- Tomaszewski JE, "Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study", Urology, 57(6 Suppl 1), pp.67~81 (2001)
- Hauser PJ, "Abnormal expression of differentiation related proteins and proteoglycan core proteins in the urothelium of patients with interstitial cystitis", J Urol, 179, pp.764~769 (2008)
- Slobodov G, "Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis", J Urol, 171, pp.1554~1558 (2004)
- Shin K, "Hedgehog", Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder, 2011, pp.472, 110~114
- Pignon JC, "p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia", Proc Natl Acad Sci U S A, 110, pp.8105~8110 (2013)
- Laguna P, "Keratin expression profiling of transitional epithelium in the painful bladder syndrome", interstitial cystitis, 2006, pp.125, 105~110
- Jhang JF, "Intravesical injections of platelet-rich plasma is effective and safe in treatment of interstitial cystitis refractory to conventional treatment-A prospective clinical trial", Neurourol Urodyn, 38, pp.703~709 (2019)
- Propert KJ, "Responsiveness of symptom scales for interstitial cystitis", Urology, 67, pp.55~59 (2006)
- Chuang FC, "Increased urothelial cell apoptosis and chronic inflammation are associated with recurrent urinary tract infection in women", PLoS One, 8, pp.e63760~ (2013)
- Kullmann FA, "Urothelial proliferation and regeneration after spinal cord injury", Am J Physiol Renal Physiol, 313, pp.F85~102 (2017)
- Jhang JF, "Electron microscopic characteristics of interstitial cystitis", bladder pain syndrome and their association with clinical condition, 2018, pp.13, e0198816~
- Kreft ME, "Urothelial injuries and the early wound healing response : tight junctions and urothelial cytodifferentiation", Histochem Cell Biol, 123, pp.529~539 (2005)
- Etulain J, "Platelets in wound healing and regenerative medicine", Platelets, 29, pp.556~568 (2018)
- Mussano F, "Cytokine, chemokine, and growth factor profile of platelet-rich plasma", Platelets, 27, pp.467~471 (2016)
- Kuffler DP, "Platelet-rich plasma and the elimination of neuropathic pain", Mol Neurobiol, 48, pp.315~332 (2013)
- Furuta A, "Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation, overactivity, and nociception in a chemically induced interstitial cystitis-like rat model", Int Urogynecol J, 29, pp.1615~1622 (2018)
- Jiang YH, "Repeated intravesical injections of platelet-rich plasma improve symptoms and alter urinary functional proteins in patients with refractory interstitial cystitis", Sci Rep, 10, pp.15218~ (2020)
- Li S, "The regulatory effects of transforming growth factor-beta on nerve regeneration", Cell Transplant, 26, pp.381~394 (2017)
