| Authors |
Hanna-Mitchell AT, Ruiz GW, Daneshgari F, Liu G, Apodaca G, Birder LA
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| Submitted By |
Lori Birder on 3/7/2013 |
| Status |
Published |
| Journal |
American journal of physiology. Regulatory, integrative and comparative physiology |
| Year |
2013 |
| Date Published |
1/15/2013 |
| Volume : Pages |
304 : R84 - R93 |
| PubMed Reference |
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| Abstract |
Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes
mellitus (DM), is characterized by a broad spectrum of symptoms including
urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late,
it is important to understand the chronic impact of DM on bladder tissues. While
changes in bladder smooth muscle and innervation have been reported in diabetic
patients, the impact of DM on the specialized epithelial lining of the urinary
bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain
reaction analysis and electron microscopy were used to evaluate UT gene
expression and cell morphology 3, 9, and 20 wk following streptozotocin (STZ)
induction of DM in female Sprague-Dawley rats compared with age-matched control
tissue. Desquamation of superficial (umbrella) cells was noted at 9 wk DM,
indicating a possible breach in barrier function. One causative factor may be
metabolic burden due to chronic hyperglycemia, suggested by upregulation of the
polyol pathway and glucose transport genes in DM UT. While superficial UT
repopulation occurred by 20 wk DM, the phenotype was different, with significant
upregulation of receptors associated with UT mechanosensation (transient
receptor potential vanilloid subfamily member 1; TRPV1) and UT
autocrine/paracrine signaling (acetylcholine receptors AChR-M2 and -M3,
purinergic receptors P2X(2) and P2X(3)). Compromised barrier function and
alterations in UT mechanosensitivity and cell signaling could contribute to
bladder instability, hyperactivity, and altered bladder sensation by modulating
activity of afferent nerve endings, which appose the urothelium. Our results
show that DM impacts urothelial homeostasis and may contribute to the underlying
mechanisms of DBD.
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