Pelvic organ prolapse is associated with alteration of sphingosine-1-phosphate/Rho-kinase signalling pathway in human vaginal wall

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, whi...

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Bibliographic Details
Published in:Journal of obstetrics and gynaecology 2015-10, Vol.35 (7), p.726-732
Main Authors: Rhee, S. H., Zhang, P., Hunter, K., Mama, S. T., Caraballo, R., Holzberg, A. S., Seftel, R. H., Seftel, A. D., Echols, K. T., DiSanto, M. E.
Format: Article
Language:English
Subjects:
Adult
Aged
Apoptosis
Case-Control Studies
elastic fibre assembly pathway
Female
Gynecology
Humans
Isoenzymes
Kinases
Lysophospholipids - metabolism
Middle Aged
pelvic organ prolapse
Pelvic Organ Prolapse - genetics
Pelvic Organ Prolapse - metabolism
Receptors, Lysosphingolipid - genetics
rho-Associated Kinases - genetics
rho-Associated Kinases - metabolism
rhoA GTP-Binding Protein - genetics
RhoA/Rho-kinase
RNA, Messenger - metabolism
Signal Transduction
Sphingosine - analogs & derivatives
Sphingosine - metabolism
sphingosine-1-phosphate
Urogenital system
Vagina - metabolism
vaginal wall tissue
Women
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Summary: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.
ISSN:0144-3615
1364-6893
DOI:10.3109/01443615.2015.1004527