RT Journal Article
SR Electronic
T1 SPHK1/S1PR1/PPAR-α axis restores TJs between uroepithelium providing new ideas for IC/BPS treatment
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202402957
DO 10.26508/lsa.202402957
VO 8
IS 2
A1 Zhang, Junjie
A1 Ge, Qingyu
A1 Du, Tianpeng
A1 Kuang, Yuhao
A1 Fan, Zongyao
A1 Jia, Xinyi
A1 Gu, Wenjin
A1 Chen, Zhengsen
A1 Wei, Zhongqing
A1 Shen, Baixin
YR 2025
UL https://www.life-science-alliance.org/content/8/2/e202402957.abstract
AB 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 elucidated S1P’s protective effects and its role as a primary messenger through SPHK1 and S1P receptor 1 (S1PR1) knockdown. This study identifies a novel mechanism whereby S1P binding to S1PR1 activates the PPAR-α pathway, thereby enhancing cholesterol transport and restoring tight junctions between uroepithelial cells. These findings elucidate the regulatory role of S1P in the bladder epithelial barrier and highlight a promising therapeutic target for IC/BPS.All data needed to evaluate the conclusions in the article are present in the article and the Supplementary Materials. Additional data related to this article may be requested from the authors.