A MAPP network study

Overexpression of tumor necrosis factor-α in mouse urothelium mimics interstitial cystitis

Wenbin Yang, Timothy J Searl, Ryan Yaggie, Anthony J Schaeffer, David Klumpp*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Interstitial cystitis/bladder pain syndrome is a chronic bladder condition associated with pain and voiding dysfunction that is often regarded as a neurogenic cystitis. Patient symptoms are correlated with the presence of urothelial lesions. We previously characterized a murine neurogenic cystitis model that recapitulates mast cell accumulation and urothelial lesions, and these events were dependent on TNF. To further explore the role of TNF in bladder inflammation and function, we generated a transgenic mouse model with chronic TNF overexpression in urothelium under the control of the uroplakin II (UPII) promoter. Transgenic mouse lines were maintained by backcross onto wild-type C57BL/6J mice and evaluated for pelvic tactile allodynia as a measure of visceral pain, urinary function, and urothelial lesions. TNF mRNA and protein were expressed at greater levels in bladders of UPII-TNF mice than in those of wild-type mice. UPII-TNF mice showed significantly increased urinary frequency and decreased void volume. UPII-TNF mice had increased urothelial apoptosis and loss of urothelial integrity consistent with urothelial lesions. Overexpression of TNF was also associated with pelvic tactile allodynia. Consistent with these findings, UPII-TNF mice exhibited increased bladder afferent activity in response to stretch ex vivo. In summary, UPII-TNF mice display significant pelvic pain, voiding dysfunction, urothelial lesions, and sensory input. Thus UPII-TNF mice are a model for characterizing mechanisms of interstitial cystitis symptoms and evaluating therapies.

Original languageEnglish (US)
Pages (from-to)F36-F44
JournalAmerican Journal of Physiology - Renal Physiology
Volume315
Issue number1
DOIs
StatePublished - Jul 1 2018

Fingerprint

Interstitial Cystitis
Urothelium
Tumor Necrosis Factor-alpha
Urinary Bladder
Cystitis
Hyperalgesia
Transgenic Mice
Uroplakin II
Visceral Pain
Pain
Pelvic Pain
Inbred C57BL Mouse
Mast Cells
Mouse Upk2 protein
Apoptosis
Inflammation
Messenger RNA
Proteins

Keywords

  • Interstitial cystitis
  • Pelvic pain
  • TNF
  • Transgenic mouse model

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

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title = "A MAPP network study: Overexpression of tumor necrosis factor-α in mouse urothelium mimics interstitial cystitis",
abstract = "Interstitial cystitis/bladder pain syndrome is a chronic bladder condition associated with pain and voiding dysfunction that is often regarded as a neurogenic cystitis. Patient symptoms are correlated with the presence of urothelial lesions. We previously characterized a murine neurogenic cystitis model that recapitulates mast cell accumulation and urothelial lesions, and these events were dependent on TNF. To further explore the role of TNF in bladder inflammation and function, we generated a transgenic mouse model with chronic TNF overexpression in urothelium under the control of the uroplakin II (UPII) promoter. Transgenic mouse lines were maintained by backcross onto wild-type C57BL/6J mice and evaluated for pelvic tactile allodynia as a measure of visceral pain, urinary function, and urothelial lesions. TNF mRNA and protein were expressed at greater levels in bladders of UPII-TNF mice than in those of wild-type mice. UPII-TNF mice showed significantly increased urinary frequency and decreased void volume. UPII-TNF mice had increased urothelial apoptosis and loss of urothelial integrity consistent with urothelial lesions. Overexpression of TNF was also associated with pelvic tactile allodynia. Consistent with these findings, UPII-TNF mice exhibited increased bladder afferent activity in response to stretch ex vivo. In summary, UPII-TNF mice display significant pelvic pain, voiding dysfunction, urothelial lesions, and sensory input. Thus UPII-TNF mice are a model for characterizing mechanisms of interstitial cystitis symptoms and evaluating therapies.",
keywords = "Interstitial cystitis, Pelvic pain, TNF, Transgenic mouse model",
author = "Wenbin Yang and Searl, {Timothy J} and Ryan Yaggie and Schaeffer, {Anthony J} and David Klumpp",
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language = "English (US)",
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T2 - Overexpression of tumor necrosis factor-α in mouse urothelium mimics interstitial cystitis

AU - Yang, Wenbin

AU - Searl, Timothy J

AU - Yaggie, Ryan

AU - Schaeffer, Anthony J

AU - Klumpp, David

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Interstitial cystitis/bladder pain syndrome is a chronic bladder condition associated with pain and voiding dysfunction that is often regarded as a neurogenic cystitis. Patient symptoms are correlated with the presence of urothelial lesions. We previously characterized a murine neurogenic cystitis model that recapitulates mast cell accumulation and urothelial lesions, and these events were dependent on TNF. To further explore the role of TNF in bladder inflammation and function, we generated a transgenic mouse model with chronic TNF overexpression in urothelium under the control of the uroplakin II (UPII) promoter. Transgenic mouse lines were maintained by backcross onto wild-type C57BL/6J mice and evaluated for pelvic tactile allodynia as a measure of visceral pain, urinary function, and urothelial lesions. TNF mRNA and protein were expressed at greater levels in bladders of UPII-TNF mice than in those of wild-type mice. UPII-TNF mice showed significantly increased urinary frequency and decreased void volume. UPII-TNF mice had increased urothelial apoptosis and loss of urothelial integrity consistent with urothelial lesions. Overexpression of TNF was also associated with pelvic tactile allodynia. Consistent with these findings, UPII-TNF mice exhibited increased bladder afferent activity in response to stretch ex vivo. In summary, UPII-TNF mice display significant pelvic pain, voiding dysfunction, urothelial lesions, and sensory input. Thus UPII-TNF mice are a model for characterizing mechanisms of interstitial cystitis symptoms and evaluating therapies.

AB - Interstitial cystitis/bladder pain syndrome is a chronic bladder condition associated with pain and voiding dysfunction that is often regarded as a neurogenic cystitis. Patient symptoms are correlated with the presence of urothelial lesions. We previously characterized a murine neurogenic cystitis model that recapitulates mast cell accumulation and urothelial lesions, and these events were dependent on TNF. To further explore the role of TNF in bladder inflammation and function, we generated a transgenic mouse model with chronic TNF overexpression in urothelium under the control of the uroplakin II (UPII) promoter. Transgenic mouse lines were maintained by backcross onto wild-type C57BL/6J mice and evaluated for pelvic tactile allodynia as a measure of visceral pain, urinary function, and urothelial lesions. TNF mRNA and protein were expressed at greater levels in bladders of UPII-TNF mice than in those of wild-type mice. UPII-TNF mice showed significantly increased urinary frequency and decreased void volume. UPII-TNF mice had increased urothelial apoptosis and loss of urothelial integrity consistent with urothelial lesions. Overexpression of TNF was also associated with pelvic tactile allodynia. Consistent with these findings, UPII-TNF mice exhibited increased bladder afferent activity in response to stretch ex vivo. In summary, UPII-TNF mice display significant pelvic pain, voiding dysfunction, urothelial lesions, and sensory input. Thus UPII-TNF mice are a model for characterizing mechanisms of interstitial cystitis symptoms and evaluating therapies.

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KW - Pelvic pain

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