Fibrosis and the bladder, implications for function ICI-RS 2017.

[AIMS] Most benign bladder pathologies are associated with an increase of extracellular matrix (ECM-fibrosis) and may progress from formation of stiffer matrix to a more compliant structure. The aims were to summarize current knowledge of the origins of bladder fibrosis and consequences in bladder function.

[METHODS] A meeting at the International Consultation on Incontinence Research Society 2017 congress discussed the above aims and considered paradigms to reduce the extent of fibrosis. Discussants based their arguments on the basis of their own expertise, supplemented by review of the literature through PubMed. Proposals for future work were derived from the discussion.

[RESULTS] Altered urodynamic compliance when ECM deposition is increased is mirrored by changes in the elastic modulus of isolated tissue, whether compliance is decreased or increased. No changes to compliance or fibrosis have been reported after botulinum toxin injections. Several paracrine and autocrine agents increase ECM deposition, the role of TGF-β was particularly emphasized. None of these agents has a net long-term effect on detrusor contractility and the reduction of contractile performance with increased ECM is due solely to a loss of detrusor mass. Several strategies to reduce fibrosis were described, ranging from potential therapeutic roles for vitamin-D or endostatin, manipulation of intracellular pathways that mediate myofibroblast differentiation and the potential role of the anti-fibrotic hormone relaxin. An understanding of epigenetic regulation of ECM deposition was also considered.

[CONCLUSIONS] The conclusion that reduced bladder contractile function with increased fibrosis is due largely to the replacement of detrusor with ECM offers a way forward for future research to consider approaches that will restore bladder function by reducing ECM deposition.