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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-6-25
pubmed:abstractText
Overactive bladder is a highly prevalent clinical condition that is often caused by bladder outlet obstruction (BOO). Increased coupling of bladder smooth muscle cells (BSMC) via gap junctions has been hypothesized as a mechanism for myogenic bladder overactivity in BOO, although little is known about the regulatory system underlying such changes. Here, we report the involvement of basic fibroblast growth factor (bFGF) and connexin 43, a bladder gap junction protein, in bladder overactivity. BOO created by urethral constriction in rats resulted in elevated bFGF and connexin 43 levels in the bladder urothelium and muscle layer, respectively, and muscle strips from these bladders were more sensitive than those from sham-operated controls to a cholinergic agonist. In vitro bFGF treatment increased connexin 43 expression in cultured rat BSMC via the ERK 1/2 pathway. This finding was supported by another in vivo model, where bFGF released from gelatin hydrogels fixed on rat bladder walls caused connexin 43 upregulation and gap junction formation in the muscle layer. Bladder muscle strips in this model showed increased sensitivity to a cholinergic agonist that was blocked by inhibition of gap junction function with alpha-glycyrrhetinic acid. Cystometric analyses of this model showed typical features of detrusor overactivity such as significantly increased micturition frequency and decreased bladder capacity. These findings suggest that bFGF from the urothelium could induce bladder hypersensitivity to acetylcholine via gap junction generation in the smooth muscle, thereby contributing to the myogenic overactivity of obstructed bladders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F46-54
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle.
pubmed:affiliation
Department of Urology, Graduate School of Medicine, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 606-8507 Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't