OBJECTIVE: Uroplakins are the protein building blocks of urothelial plaques that cover the urothelium. We are here to demonstrate that uroplain expressio is up-regulated in endometriosis and that uroplakin is a downstream target of HOXA10 transcriptional repression in endometrium. DESIGN: IHC and RT-PCR identification of UP IIIb in endometrial tissue from patient with and without endometriosis. MATERIALS AND METHODS: Endometrial samples were collected via Pipelle sampling from 30 patients with and without endometriosis in the mid-secretory phase under an approved HIC protocol. An aliqout of tissue was frozen for RNA extraction and subsequent RT-PCR, while a second aliquot was fixed for IHC. Real time RT-PCR was performed. Transfection of endometrial cells with pcDNA-HOXA10 used to determine HOXA10 dependent expression. RESULTS: Human endometrium expressed small amounts of UP IIIb mRNA as demonstrated by RT-PCR and IHC. Endometrium from patients with endometriosis expressed significant higher levels of UPIIIb mRNA compared to endometrial samples from patients without endometriosis 6 fold (P<0.001). Transfection of Ishikawa cells with a HOXA10 expression construct led to 2.9 fold lower (P<0.01) levels of UP IIIb expression. CONCLUSION: Here we demonstrated uroplakin expression in human endometrium and also its increased expression in eutopic endometrium from women with endometriosis. We show that UPIIIb is a downstream target of HOXA10 transcriptional regulation in endometrium. UPIIIb is repressed by HOXA10 in normal endometrium; however in patients with endometriosis, where HOXA10 expression is low, UPIIIb expression is dramatically up-regulated, which results in an increase expression of UPIIIb in endometrium of women with endometriosis compared to normal endometrium samples. The underlying mechanism of this barrier molecule may provide a protective barrier in the ectopic endometrium that prevents immune recognition and elimination in the peritoneal cavity.
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