The Expression And Role Of TWEAK In The Endometriosis

Objective:It has been suggested that TNF-like weak inducer of apoptosis(TWEAK) could transmit death signal and involve in the apoptosis of cells after binding with its specific receptor.It plays a key role in the process of inducing the death of carcinoma cells,inhibiting the growth of tumor and maintaining the immune system's equilibrium.Fibroblast growth factor-inducible 14(Fn-14),binding to TWEAK specifically and involving in the cellular apopotosis,is its main receptor.In this study, the expression of TWEAK mRNA and protein were investigated on the eutopic and ectopic endometrium from patients with endometriosis.Besides,the effect of the estrogen and progesterone on the expression of TWEAK in the endometrial stromal cells was evaluated too.Both of the two parts are designed to investigate the mechanism of TWEAK's role and whether it involves in the development of endometriosis,and whether there might be some potential therapeutic targets for treatment convention.Methods and Materials:1.Eutopic and ectopic endometrium tissues were obtained from patients with endometriosis(ovarian endometrioid cysts and adenomyosis) undergoing laparoscopy and hysterectomy.The endometrium from the patients without endometriosis was collected as the control group.The concentrations of TWEAK expression were investigated on all the types of endometrium,employing real-time PCR,Immunohistochemistry and Western Blot assay.2.Various concentrations of estrogen and progesterone were added to the culture medium of endometrial stromal cells.Collect cells from these culture mediums and identify the expression of TWEAK using RT-PCR and in cell western blot.Results:1.TWEAK and Fn-14 were indeed expressed on the endometrium of women, including the eutopic and ectopic endometrium from the patients with endometriosis,as well as the endometrium from those without endometriosis.2.TWEAK protein was found both in the cytoplasm of glandular epithelium cells and stromal cells of endometrium.3.TWEAK expression on both eutopic endometrium and control endometrium in secretory phase is higher than that of proliferative phase.4.The average relative TWEAK mRNA and protein abundance on ectopic endometrium was much lower than that of eutopic and control endometrium after normalization.5.The expression of TWEAK in the endometrial stromal cells was influenced by estrogen,and it varied according to the concentrations of estrogen.6.The expression of TWEAK in the endometrial stromal cells was influenced by progesterone,and it is upregulated as the concentrations of progesterone decreased.7.The expression of TWEAK in the endometrial stromal cells could be influenced by both estrogen and progesterone simultaneously.However,no significant difference on the expression of TWEAK in the ESC could be shown between the group that treated by estrogen and progesterone and the one that only treated by progesterone alone.Conclusion:1.TWEAK and Fn-14 are expressed on the endometrium of women.The concentration of TWEAK expression is upregulated in secretory phase during the menstruation,and it might involve in the apoptosis of endometrial cells.2.The low expression of TWEAK on the ectopic endometrium from the patients with endometriosis might have led to a decrease in apoptosis of endometrial cells.3.The expression of TWEAK in the ESC could be influenced by estrogen and progesterone,and its function may be regulated by these two steroid hormones in the development of endometriosis.