SPHK1/S1PR1/PPAR-α axis restores TJs between uroepithelium providing new ideas for IC/BPS treatment.

ABSTRACT: Interstitial cystitis/bladder pain syndrome (IC/BPS) represents a chronic, aseptic inflammatory bladder condition with an unclear etiology and few therapeutic options. A composite barrier structure composed of the uroepithelium and glycosaminoglycan layer forms on the bladder's inner surface to block urine and other harmful substances. Dysfunction of this barrier may initiate the pathogenesis of IC/BPS. Sphingosine-1-phosphate (S1P) plays a crucial role in forming tight junctions. Perfusion of S1P into the bladder restored uroepithelial tight junctions in mice with cyclophosphamide-induced acute cystitis and ameliorated symptoms of the lower urinary tract. Mice lacking sphingosine kinase 1 (SHPK1) exhibited more severe bladder injuries and dysfunction. Concurrent in vitro experiments eluci

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11584326 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature