RESUMO
Growth arrest specific protein 6 (GAS6) plays an important role in the occurrence and development of tumors, and its signal transduction is involved in cell proliferation, adhesion and migration, but its related functions and molecular mechanisms in endometriosis (EMs) are still unclear. In this study, we searched and downloaded the transcriptome datasets of EMs from GEO database and performed GEO online analysis, and then screened out the differentially expressed genes and performed cluster analysis based on GO and KEGG pathway. The mRNA levels of the differentially expressed genes shared by more than three datasets were verified by qRT-PCR in the endometrium of ten women with no endometriosis and no clear disease and the ectopic endometrium of 11 patients with ovarian chocolate cysts. Immunohistochemistry and qRT-PCR were used to verify the expression of GAS6 and epithelial mesenchymal transition (EMT) marker genes, and immunofluorescence was used to co-label GAS6 and E-cadherin in endometriosis clinical samples. In this study, a total of 47 differentially expressed genes were screened out of the four transcriptome datasets, which were mainly enriched in processes such as cell migration and related signal pathways such as MAPK, PI3K-AKT, and tight junction. The mRNA levels of the nine differentially expressed genes shared by more than three datasets in endometriosis patients were consistent with the results of bioinformatics analysis. GAS6 expression levels in ectopic endometrium of EMs patients are higher than the control group (P < 0. 05), and EMs patients have the characteristics of EMT in the ectopic endometrial tissue, that is, the expression of E-cadherin is down-regulated (P < 0. 05) and the expression of vimentin is up-regulated (P < 0. 01). The expression of E-cadherin in the ectopic endometrial glandular epithelial cells of EMs patients is low while the expression of GAS6 is up-regulated, suggesting that GAS6 may mediate the EMT process in endometriosis. In conclusion, this study reveals that GAS6 is highly expressed in endometriosis patients and may mediate the EMT process to participate in the occurrence and development of endometriosis, providing a potential target for clinical treatment of endometriosis.
RESUMO
Objective To study the relationship between syncytiotrophoblast microvillous membrane (STBM) shedding in severe preeclampsia (sPE) and placenta Rho/ROCK molecule expression. Methods In this study, placenta tissue of 20 sPE lying-in women (sPE group) and 20 normal lying-in women (control group) were collected. The syncytiotrophoblast microvillous structure of the placenta tissue was scrutinized with transmission electron microscope (TEM). The microvillous numerical density (Nv), surface density (Sv), and volume density (Vv) of the cell surfaces were analyzed with stereology method. Western blotting and immunohistochemistry were used to detect the expression of Rho subfamily proteins (RhoA, RhoB, RhoC) and Rho kinases (ROCKI, ROCKII) in the placenta tissues. The correlation of the expression of Rho, ROCK proteins, and the shedding of STBM was examined with Spearman rank correlation analysis. Results The Nv, Sv, and Vv of the syncytiotrophoblast microvillous membranes in sPE group were significantly less than those of the control group (P<0.05). Compared with the control group, the expression levels of RhoA, RhoB, ROCKI, and ROCKII proteins in sPE group were noticeably elevated (P<0.05). In sPE group, the expressions of RhoB, ROCKI, and ROCKII proteins were positively correlated with the shedding of STBM (r=0.631, r=0.826, r=0.865, P<0.05). Conclusion The signaling pathways constituted by RhoB and its downstream molecules ROCKI/ROCKII, may play an important regulatory role in the upregulation of STBM shedding in sPE.