title: A novel role for follistatin in hypersensitivity following cystitis.
abstract: 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.
  
  
  
  Adult female C57BL/6 mice were treated with CYP (100 mg/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.
  
  
  
  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.
  
  
  
  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. 36:286-292, 2017. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Anesthesiology, Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Amber D
authors.initials: AD
authors.lastname: Shaffer
authors.affiliation: Department of Anesthesiology, Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: La
authors.affiliation: Department of Anesthesiology, Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Sonali C
authors.initials: SC
authors.lastname: Joyce
authors.affiliation: Department of Anesthesiology, Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: G F
authors.initials: GF
authors.lastname: Gebhart
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D005260:Female; D038681:Follistatin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D038681:Follistatin; D003520:Cyclophosphamide
keywords: activins; cyclophosphamide; interstitial cystitis; single-fiber recording; transforming growth factor beta; visceral pain