Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment.
BACKGROUND
An increasing body of evidence suggests a possible role of suburothelial myofibroblasts (MFs) in bladder mechanosensation and in the pathophysiology of detrusor overactivity (DO).


OBJECTIVE
To determine whether markers of MFs, including gap junction protein connexin43 (Cx43) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO (NDO) or idiopathic DO (IDO) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A (BoNTA).


METHODS
Patients with NDO (n=10) or IDO (n=11) were treated in a single-centre, open-label study of intradetrusor BoNTA injections. Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder (OAB) symptoms. This study is registered with ClinicalTrials.gov, number NCT00662064.


METHODS
Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment. They were studied with quantitative immunofluorescence using antibodies to connexin 43 (Cx43), vimentin, and c-kit.


METHODS
Differences in Cx43, vimentin, and c-kit immunoreactivity between control subjects and NDO or IDO patients (primary outcomes). Changes in NDO or IDO, Cx43 immunoreactivity, and c-kit immunoreactivity after BoNTA treatment (secondary outcomes).


CONCLUSIONS
Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls, but remained unchanged after BoNTA treatment. C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment.


CONCLUSIONS
Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO. It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality. Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs.
Roosen
Alexander
A
Institute of Neurology, National Hospital for Neurology and Neurosurgery, University College London, UK.
Datta
Soumendra N
SN
Chowdhury
Rasheda A
RA
Patel
Pravina M
PM
Kalsi
Vinay
V
Elneil
Sohier
S
Dasgupta
Prokar
P
Kessler
Thomas M
TM
Khan
Shahid
S
Panicker
Jalesh
J
Fry
Christopher H
CH
Brandner
Sebastian
S
Fowler
Clare J
CJ
Apostolidis
Apostolos
A
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D018031:Connexin 43 / Q000187:drug effects / Q000378:metabolism*; D003558:Cystoscopy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000008:administration & dosage*; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014563:Urodynamics / Q000187:drug effects; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D018031:Connexin 43; D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A