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Overexpression of a steroid receptor-binding protein bearing the regulator of the G-protein signaling domain suppresses migration and invasion of human endometrial stromal cells stimulated by 17β-estradiol

  • Yu-fang Xiong
    Affiliations
    Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
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  • Zhou-fang Xiong
    Correspondence
    Corresponding author. Tel.: +86 13871079902; fax: +86 02785351649.
    Affiliations
    Department of Obstetrics and Gynecology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China
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Published:November 24, 2015DOI:https://doi.org/10.1016/j.ejogrb.2015.11.019

      Abstract

      Objective

      Endometriosis is an estrogen-dependent disease, a steroid receptor-binding protein bearing the regulator of the G-protein signaling domain (SRB-RGS) can suppress the estrogen receptors-mediated transcriptional activities. We sought to determine whether overexpression of SRB-RGS suppresses the migration and invasion ability of endometrial stromal cells stimulated by 17β-estradiol (E2).

      Study Design

      Endometrial stromal cells were obtained from endometriosis patients. SRB-RGS was overexpressed in the cells stimulated by E2. The migration and invasion ability of the cells were measured by migration assay and invasion assay, respectively. Western blot analysis was done to test the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF).

      Results

      Overexpression of SRB-RGS suppressed the migration and invasion ability of the stromal cells stimulated by E2; it also suppressed the expression of MMP-9 and VEGF, while the expression of TIMP-1 was increased.

      Conclusions

      Overexpression of SRB-RGS suppresses the migration and invasion ability of the E2-stimulated endometrial stromal cells. The molecular mechanism is the reduced expression of MMP-9 and VEGF, and the increased expression of TIMP-1. These findings suggest that the coding gene of SRB-RGS is a promising target gene for endometriosis gene therapy.

      Keywords

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      References

        • Bulun S.E.
        Endometriosis.
        N Engl J Med. 2009; 360: 268-279
        • Collette T.
        • Maheux R.
        • Mailloux J.
        • Akoum A.
        Increased expression of matrix metalloproteinase-9 in the eutopic endometrial tissue of women with endometriosis.
        Hum Reprod. 2006; 21: 3059-3067
        • Hu X.
        • Li D.
        • Zhang W.
        • Zhou J.
        • Tang B.
        • Li L.
        Matrix metalloproteinase-9 expression correlates with prognosis and involved in ovarian cancer cell invasion.
        Arch Gynecol Obstet. 2012; 286: 1537-1543
        • Singh A.K.
        • Chattopadhyay R.
        • Chakravarty B.
        • Chaudhury K.
        Altered circulating levels of matrix metalloproteinases 2 and 9 and their inhibitors and effect of progesterone supplementation in women with endometriosis undergoing in vitro fertilization.
        Fertil Steril. 2013; 100: 127-134
        • Huhtinen K.
        • Stahle M.
        • Perheentupa A.
        • Poutanen M.
        Estrogen biosynthesis and signaling in endometriosis.
        Mol Cell Endocrinol. 2012; 358: 146-154
        • Rocha A.L.
        • Reis F.M.
        • Taylor R.N.
        Angiogenesis and endometriosis.
        Obstet Gynecol Int. 2013; 2013: 859619
        • Hyder S.M.
        • Nawaz Z.
        • Chiappetta C.
        • Stancel G.M.
        Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor.
        Cancer Res. 2000; 60: 3183-3190
        • Kianpour M.
        • Nematbakhsh M.
        • Ahmadi S.M.
        • et al.
        Serum and peritoneal fluid levels of vascular endothelial growth factor in women with endometriosis.
        Int J Fertil Steril. 2013; 7: 96-99
        • Vignali M.
        • Bianchi S.
        • Candiani M.
        • Spadaccini G.
        • Oggioni G.
        • Busacca M.
        Surgical treatment of deep endometriosis and risk of recurrence.
        J Minim Invasive Gynecol. 2005; 12: 508-513
        • Mounsey A.L.
        • Wilgus A.
        • Slawson D.C.
        Diagnosis and management of endometriosis.
        Am Fam Physician. 2006; 74: 594-600
        • Ikeda M.
        • Hirokawa M.
        • Satani N.
        • et al.
        Molecular cloning and characterization of a steroid receptor-binding regulator of G-protein signaling protein cDNA.
        Gene. 2001; 273: 207-214
        • Ikeda M.
        • Inoue S.
        • Muramatsu M.
        • Minatogawa Y.
        Characterization and identification of a steroid receptor-binding protein, SRB-RGS.
        Biol Pharm Bull. 2007; 30: 1056-1064
        • Nasu K.
        • Nishida M.
        • Ueda T.
        • et al.
        Bufalin induces apoptosis and the G0/G1 cell cycle arrest of endometriotic stromal cells: a promising agent for the treatment of endometriosis.
        Mol Hum Reprod. 2005; 11: 817-823
        • Wang Y.
        • Yu J.
        • Luo X.
        • et al.
        Abnormal regulation of chemokine TECK and its receptor CCR9 in the endometriotic milieu is involved in pathogenesis of endometriosis by way of enhancing invasiveness of endometrial stromal cells.
        Cell Mol Immunol. 2010; 7: 51-60
        • Daniel E.M.
        • Plinio T.B.
        • Celia Y.P.
        • Luiz E.N.
        Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases.
        J Exp Clin Cancer Res. 2010; 29: 4
        • Jiao L.
        • Qi X.
        • Lu G.
        • Zhang Q.
        • Zhang C.
        • Gao J.
        Effect of traditional Chinese medicine (Xiaochaihu Tang) on the expression of MMP-2 and MMP-9 in rats with endometriosis.
        Exp Ther Med. 2013; 6: 1385-1389
        • Singh A.K.
        • Chattopadhyay R.
        • Chakravarty B.
        • Chaudhury K.
        Altered circulating levels of matrix metalloproteinases 2 and 9 and their inhibitors and effect of progesterone supplementation in women with endometriosis undergoing in vitro fertilization.
        Fertil Steril. 2013; 100: 127-134
        • Song W.-W.
        • Lu H.
        • Hou W.-J.
        • et al.
        Expression of vascular endothelial growth factor C and anti-angiogenesis therapy in endometriosis.
        Int J Clin Exp Pathol. 2014; 7: 7752-7759