GnRH agonists induce endometrial epithelial cell apoptosis via GRP78 down-regulation

Journal of Translational Medicine

Yifeng Wang¹  Li Li²  Shuiwang Hu³  Fenghua Liu²  Huinan Weng² 

[1] ZhuJiang Hospital of Southern Medical University, Guangzhou, China;GuangDong Women and Children Hospital, Guangzhou, China;Department of Pathophysiology, Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou, China

关键词: GRP78;    Proteomics;    Gonadotropin-releasing hormone agonist;    Eutopic endometrium;    Endometriosis;   

Others  :  1147356
DOI  :  10.1186/s12967-014-0306-y

 received in 2014-06-17, accepted in 2014-10-21,  发布年份 2014

【 摘 要 】

Background

Endometriosis is a benign chronic gynecological disease that affects women of reproductive age, characterized by the presence of functional endometrial tissues outside the uterine cavity. GnRH agonists exhibit anti-proliferative and apoptosis-enhancing activities and have long been used for the treatment of endometriosis. There is a critical need to identify the signaling modules involving GnRH agonist therapy for the treatment of endometriosis. In this study, we compared the proteomic profiles of endometriosis in patients before and after GnRH agonist therapy to identify proteins that might provide further information concerning the mechanisms underlying the functions of GnRH agonists.

Methods

A total of 55 protein spots with different abundances were observed using Difference Gel Electrophoresis (DIGE), and 26 of these proteins were assigned clear identities through Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Tandem Mass Spectroscopy (MALDI-TOF/TOF MS).

Results

We validated four of these proteins through Western blotting and immunohistochemistry using human endometrial tissue. We also characterized the effect of Leuprolide acetate (LA) on the apoptosis of eutopic endometrial epithelial cells. LA treatment significantly promoted the apoptosis of eutopic endometrial epithelial cells and inhibited the expression of the anti-apoptotic factor GRP78. GRP78 knockdown enhanced LA-induced cell apoptosis, whereas, the overexpression of GRP78 in eutopic endometrial epithelial cells suppresses LA-induced apoptosis.

Conclusion

These results suggest that GnRH agonists induce endometrial epithelial cell apoptosis via GRP78 down-regulation. This study might provide an important molecular framework for further evaluation of GnRH agonist therapy.

【 授权许可】

   
2014 Weng et al.; licensee BioMed Central Ltd.

【 图 表 】

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