title: Pelvic organ prolapse is associated with alteration of sphingosine-1-phosphate/Rho-kinase signalling pathway in human vaginal wall.
abstract: Pelvic organ prolapse (POP) is a debilitating condition of unknown aetiology affecting > 50% of women over 40 years of age. In POP patients, the vaginal walls are weakened allowing descent of pelvic organs through the vagina. We sought to determine if sphingosine-1-phosphate (S1P) signalling, which regulates smooth muscle contractility and apoptosis via the RhoA/Rho-kinase (ROK) pathway, is altered in the vagina of women with POP. Utilising anterior vaginal wall specimens, we provide novel demonstration of the S1P pathway in this organ. Additionally, comparing specimens from women having pelvic reconstructive surgery for POP and control subjects, we reveal increases in mRNA expression of the three major mammalian S1P receptors (S1P1-S1P3), and RhoA and the ROK isoforms: ROKα and ROKβ in POP patients, which correlates with a decrease in elastic fibre assembly pathway constituents. Taken together, our data suggest the S1P/ROK pathway as a novel area for future POP research and potential therapeutic development.
authors.affiliation: a Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology , Cooper University Hospital , Camden , NJ , USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Rhee
authors.affiliation: b Division of Urology, Department of Surgery , Cooper University Hospital , Camden , NJ , USA.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.affiliation: a Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology , Cooper University Hospital , Camden , NJ , USA.
authors.forename: K
authors.initials: K
authors.lastname: Hunter
authors.affiliation: a Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology , Cooper University Hospital , Camden , NJ , USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Mama
authors.affiliation: a Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology , Cooper University Hospital , Camden , NJ , USA.
authors.forename: R
authors.initials: R
authors.lastname: Caraballo
authors.affiliation: a Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology , Cooper University Hospital , Camden , NJ , USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Holzberg
authors.affiliation: b Division of Urology, Department of Surgery , Cooper University Hospital , Camden , NJ , USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Seftel
authors.affiliation: b Division of Urology, Department of Surgery , Cooper University Hospital , Camden , NJ , USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Seftel
authors.affiliation: a Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology , Cooper University Hospital , Camden , NJ , USA.
authors.forename: K T
authors.initials: KT
authors.lastname: Echols
authors.affiliation: b Division of Urology, Department of Surgery , Cooper University Hospital , Camden , NJ , USA.|c Department of Biomedical Sciences , Cooper Medical School of Rowan University , Camden , NJ , USA.
authors.forename: M E
authors.initials: ME
authors.lastname: DiSanto
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007527:Isoenzymes; D008246:Lysophospholipids / Q000378:metabolism*; D008875:Middle Aged; D056887:Pelvic Organ Prolapse / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000235:genetics; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D014621:Vagina / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics
chemical_list: D007527:Isoenzymes; D008246:Lysophospholipids; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; C477522:S1PR2 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C577483:sphingosine-1-phosphate receptor-3, human; C060506:sphingosine 1-phosphate; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D013110:Sphingosine
keywords: Apoptosis; RhoA/Rho-kinase; elastic fibre assembly pathway; pelvic organ prolapse; sphingosine-1-phosphate; vaginal wall tissue