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

Whasun Lim, Hyocheol Bae, Fuller W. Bazer, Gwonhwa Song

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3295-3305
Number of pages11
JournalJournal of Cellular Physiology
Volume233
Issue number4
DOIs
Publication statusPublished - 2018 Apr

Bibliographical note

Funding Information:
This research was funded by Basic Science Research Program (2015R1D1A1A01059331) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C0929).

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Keywords

  • ER stress
  • FGF2
  • proliferation
  • uterine epithelial cells

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this