Ephrin A1 promotes proliferation of bovine endometrial cells with abundant expression of proliferating cell nuclear antigen and cyclin D1 changing the cell population at each stage of the cell cycle. Issue 4 (21st September 2018)

• Record Type: Journal Article
• Authors: Lim, Whasun; Bae, Hyocheol; Bazer, Fuller W.; Song, Gwonhwa
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 4(2019:Apr.)
• Page Start: 4864
• Page End: 4873
• Publication Date: 2018-09-21
• Subjects: cattle -- endometrial epithelial cells -- ephrin A1 -- proliferation; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27275
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Ephrin A1 has a role in a variety of biological events, including cell proliferation, differentiation, migration, and angiogenesis. Ephrin A1 expression is abundant in trophoblasts and endometrial cells during the implantation period; however, its intracellular activities have not yet been reported in bovine endometrial (BEND) epithelial cells. The aim of this study was to identify the functional role of ephrin A1 in BEND cells, which have served as a good model system for investigating the regulation of signal transduction following treatment with interferon‐τ (IFNT) in vitro. Supplementation of ephrin A1 to BEND cells increased cell proliferation and increased levels of proliferating cell nuclear antigen and cyclin D1 protein in BEND cell nuclei. To investigate intracellular mechanisms regulated by ephrin A1, we performed Western blot analysis focused on mitogen‐activated protein kinase (MAPK) and phosphoinositide 3‐kinase (PI3K) signaling, which are significantly involved in the successful maintenance of pregnancy. Ephrin A1 dose‐dependently increased phosphorylation of extracellular signal‐regulated kinases (ERK)1/2, c‐Jun N‐terminal kinases (JNK), P38, protein kinase B (AKT), P70S6K, S6, and cyclin D1, and the activated proteins were suppressed by pharmacological inhibitors including wortmannin (a PI3K inhibitor), U0126 (an ERK1/2 inhibitor), and SP600125 (a JNK inhibitor). Among ephrin A1 receptors, abundant expression of EPHA2 and EPHA4 messenger RNA was detected in BEND cells by reverse transcription polymerase chain reaction analysis. Furthermore, tunicamycin‐induced endoplasmic reticulum (ER) stress was inactivated by ephrin A1 treatment of BEND cells. Our findings suggest that ephrin A1 promotes the development of BEND cells and likely enhances uterine capacity and maintenance of pregnancy by activating MAPK and PI3K signaling cascades and by restoring ER stress. Abstract : Collectively, the results of current study demonstrate treatment of bovine endometrial (BEND) cells with ephrin A1 enhanced cell proliferation leading to abundant expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and cell cycle phase changes. These results indicate that ephrin A1 may increase implantation and maternal–fetal interaction during early pregnancy by improving uterine development and receptivity in cattle, and potentially also in other species.