A novel role for follistatin in hypersensitivity following cystitis

Amber D. Shaffer, Bin Feng, Jun-Ho La, Sonali C. Joyce, G. F. Gebhart

Research output: Contribution to journalArticle

Abstract

Aims: Previous studies have shown that the activin-binding protein follistatin reduces inflammation in several mouse models of colitis. To determine whether follistatin also has a beneficial effect following bladder inflammation, we induced cystitis in mice using cyclophosphamide (CYP) and examined the relationship between bladder hypersensitivity and bladder follistatin expression. Methods: Adult female C57BL/6 mice were treated with CYP (100mg/kg) or vehicle (saline) three times over 5 days. Bladder hypersensitivity was assessed by recording the visceromotor response (VMR) to urinary bladder distension and in vitro single-fiber bladder afferent recording. Follistatin gene expression was measured using qRT-PCR. Immunohistochemistry was employed for further characterization. Results: Bladder hypersensitivity was established by day 6 and persisted to day 14 in CYP-treated mice. On day 14, hypersensitivity was accompanied by increases in follistatin gene expression in the bladder. Follistatin-like immunoreactivity colocalized with laminin, and the percentage of structures in the lamina propria that were follistatin-positive was increased in CYP-treated mice. Exogenous follistatin increased VMR and afferent responses to bladder distension in CYP- but not vehicle-treated mice. Conclusions: Chronic bladder pain following CYP treatment is associated with increased follistatin expression in the bladder. These results suggest a novel, pro-nociceptive role for follistatin in cystitis, in contrast with its proposed therapeutic role in colitis. This protein has exciting potential as a biomarker and therapeutic target for bladder hypersensitivity. Neurourol. Urodynam.

Original languageEnglish (US)
JournalNeurourology and Urodynamics
DOIs
StateAccepted/In press - 2015
Externally publishedYes

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Keywords

  • Activins
  • Cyclophosphamide
  • Interstitial cystitis
  • Single-fiber recording
  • Transforming growth factor beta
  • Visceral pain

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology

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