Abstract
(1) Background: Endometrial regulation is a necessary condition for maintaining normal uterine physiology, which is driven by many growth factors. Growth factors produced in the endometrium are thought to be related to the proliferation of endometrial cells induced by estradiol-17β (E2). In this study, we found that E2 can induce the secretion of brain-derived neurotrophic factor (BDNF) in Ishikawa cells (the cells of an endometrial cell line). Furthermore, Ishikawa cells were used in exploring the regulatory role of BDNF in endometrial cells and to clarify the potential mechanism. (2) Methods: Ishikawa cells were treated with different concentrations of BDNF (100, 200, 300, 400, and 500 ng/mL). The mRNA expression levels of various proliferation-related genes were detected through quantitative reverse transcription polymerase chain reaction, and the expression of various proliferation-related genes was detected by knocking out BDNF or inhibiting the binding of BDNF to its receptor TrkB. The expression levels of various proliferation-related genes were detected by performing Western blotting on the TrkB-ERK1/2 signaling pathway. (3) Results: Exogenous BDNF promoted the growth of the Ishikawa cells, but the knocking down of BDNF or the inhibition of TrkB reduced their growth. Meanwhile, BDNF enhanced cell viability and increased the expression of proliferation-related genes, including cyclin D1 and cyclin E2. More importantly, the BDNF-induced proliferation of the Ishikawa cells involved the ERK1/2 signaling pathway. (4) Conclusions: The stimulating effect of exogenous E2 on the expression of BDNF in the uterus and the action of BDNF promoted the proliferation of the Ishikawa cells through the TrkB-ERK1/2 signal pathway.
Highlights
Estradiol-17β (E2) plays an important role in overall reproductive activities in mammals [1]
The results showed that E2 increased brain-derived neurotrophic factor (BDNF) level at the mRNA and protein levels (Figure 2A–C)
PD98059 (10 μM, a specific inhibitor of mitogen-activated protein kinase (MAPK), Beyotime) significantly decreased BDNF-induced cell proliferation and gene expression (Figure 6C–E). These results showed that BDNF promotes the proliferation of Ishikawa cells via the MAPK/extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway
Summary
Estradiol-17β (E2) plays an important role in overall reproductive activities in mammals [1]. The endometrium has receptor ERα, which is one of the E2 target tissues [3,4,5,6]. E2 is up-regulated during embryo implantation in humans and mice [7,8,9], and E2 can proliferate mouse uterine matrix, endometrial glandular epithelial cells, endometrial cells, and glandular epithelial cells [4,10,11]. E2 and progesterone can stimulate endometrial stromal cell proliferation [3], which is necessary for establishing and maintaining pregnancy. The endometrium loss of the E2 receptor gene results in uterine dysplasia and female infertility [12]. High concentrations of E2 can induce endometrial cell proliferation, which may lead to endometrial cancer [5,13] or endometriosis [14]
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