Fibroblast growth factor 2 induces proliferation and distribution of G2/M phase of bovine endometrial cells involving activation of PI3K/AKT and MAPK cell signaling and prevention of effects of ER stress. Issue 4 (28th September 2017)

• Record Type: Journal Article
• Authors: Lim, Whasun; Bae, Hyocheol; Bazer, Fuller W.; Song, Gwonhwa
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 4(2018:Apr.)
• Page Start: 3295
• Page End: 3305
• Publication Date: 2017-09-28
• Subjects: ER stress -- FGF2 -- proliferation -- uterine epithelial cells; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26173
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Fibroblast growth factor 2 (FGF2) is abundantly expressed in conceptuses and endometria during pregnancy in diverse animal models including domestic animals. However, its intracellular mechanism of action has not been reported for bovine endometrial cells. Therefore, the aim of this study was to identify functional roles of FGF2 in bovine endometrial (BEND) cell line which has served as a good model system for investigating regulation of signal transduction following treatment with interferon‐tau (IFNT) in vitro. Results of present study demonstrated that administration of FGF2 to BEND cells increased their proliferation and regulated the cell cycle through DNA replication by an increase of PCNA and Cyclin D1. FGF2 also increased phosphorylation of AKT, P70S6K, S6, ERK1/2, JNK, and P38 in BEND cells in a dose‐dependent manner, and expression of each of those transcription factors was inhibited by their respective pharmacological inhibitor including Wormannin, U0126, and SP600125. In addition, the increase in proliferation of BEND cells and activation of the protein kinases in response to FGF2 was suppressed by BGJ398, a FGFR inhibitor. Furthermore, proliferation of BEND cells was inhibited by tunicamycin, but treatment of BEND cells with FGF2 restored proliferation of BEND cells. Consistent with this result, the stimulated unfolded protein response (UPR) regulatory proteins induced by tunicamycin were down‐regulated by FGF2. Results of this study suggest that FGF2 promotes proliferation of BEND cells and likely enhances uterine capacity and maintenance of pregnancy by activating cell signaling via the PI3K and MAPK pathways and by restoring ER stress through the FGFR. Abstract : FGF2 induces proliferation of BEND cells that was confirmed by increases in PCNA in nuclei of BEND cells and a greater percent of BEND cells in G2 phase of the cell cycle via FGFR1 and activation of PI3K/AKT and MAPK signal transduction. In addition, inhibition of FGF2‐induced proliferation of BEND cells was inhibited by tunicamycin‐induced ER stressor proteins. These results indicate that FGF2 may act on uterine endometrial cells to increase proliferation and improve uterine functions during pregnancy.