Tzu Chi Medical Journal
Volume 21, Issue 2 , Pages 103-109, June 2009

Pathophysiology of Urothelial Dysfunction in Patients with Interstitial Cystitis/Painful Bladder Pain Syndrome: Increased Apoptosis and Decreased Junctional Protein Expression in the Urothelium due to Suburothelial Inflammation

  • Jia-Heng Shie
    • ,
  • Hann-Chorng Kuo

      Affiliations

    • Corresponding Author InformationCorresponding author. Department of Urology, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung-Yang Road, Hualien, Taiwan

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

Received 23 January 2009; received in revised form 2 February 2009; accepted 3 February 2009.

Article Outline

Abstract 

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a heterogeneous syndrome characterized by bladder pain and associated with frequency and nocturia. Recent findings have proposed several pathophysiological mechanisms including epithelial dysfunction, activation of mast cells, neurogenic inflammation, autoimmunity and occult infection. The human bladder urothelium and urothelial cells play an important role in the normal defense mechanism. One of the most common findings in IC/PBS patients is denudation or thinning of the bladder epithelium, suggesting an altered regulation of urothelial homeostasis. Urine from patients with IC/PBS has been shown to inhibit urothelial proliferation through antiproliferative factor (APF). In urine samples of IC/PBS patients, significant increases in APF, decreases in heparin-binding epidermal growth factor (HB-EGF) and increased levels of EGF were discovered. APF expressed by the urothelial cells induces increased permeability in cell culture, and regulates expression of other cytokines, including upregulation of HB-EGF and downregulation of EGF. These cytokine abnormalities were also related to increases in purinergic signaling, which mediates increased bladder sensation. Abnormal expression of uroplakin, chondroitin sulfate and tight junctional protein zonula occludens-1 (ZO-1) strongly suggests abnormal differentiation in bladders with IC/PBS, whereas elevated E-cadherin expression may represent an adaptation to increased bladder permeability. The epithelial damage may precede the other histopathologic findings in the bladder wall. A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network which integrate the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. Investigation of the relationship between chronic inflammation and urothelial dysfunction such as urothelial apoptosis, expression of junctional protein and inflammatory reactions in the suburothelium might demonstrate this hypothesis.

Keywords:  Apoptosis , Inflammation , Interstitial cystitis , Painful bladder syndrome , Urothelial dysfunction

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PII: S1016-3190(09)60020-3

doi:10.1016/S1016-3190(09)60020-3

Tzu Chi Medical Journal
Volume 21, Issue 2 , Pages 103-109, June 2009

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