Bifunctional role of ephrin A1-Eph system in stimulating cell proliferation and protecting cells from cell death through the attenuation of ER stress and inflammatory responses in bovine mammary epithelial cells
- Authors
- Kang, Minkyung; Jeong, Wooyoung; Bae, Hyocheol; Lim, Whasun; Bazer, Fuller W.; Song, Gwonhwa
- Issue Date
- 3월-2018
- Publisher
- WILEY
- Keywords
- Eph A; ephrin A1; mammary epithelial cells; mammary gland; milk production
- Citation
- JOURNAL OF CELLULAR PHYSIOLOGY, v.233, no.3, pp.2560 - 2571
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CELLULAR PHYSIOLOGY
- Volume
- 233
- Number
- 3
- Start Page
- 2560
- End Page
- 2571
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/77295
- DOI
- 10.1002/jcp.26131
- ISSN
- 0021-9541
- Abstract
- Structural and functional development of themammary gland is constant in themammary gland life cycle. Ephreceptors and their ligands, ephrins, control events through cell-to-cell interactions during embryonic development, and adult tissue homeostasis; however, little information on participation of ephrin A1, a representative ligand of the Eph receptor, in the development and function of normal mammary glands is known. In this study, we demonstrated functional effects of the ephrin A1-Eph system and mechanisms of its action on bovine mammary epithelial (MAC-T) cells. The in vitro cultured MAC-T cells expressed the ephrin A1 ligand and EphA1, A2, A4, A7, and A8 among the eight members of the Eph A family. Our results revealed that ephrin A1 induced MAC-T cell cycle progression and stimulated cell proliferation with abundant expression of nucleic PCNA and cyclin D1 proteins. Additionally, ephrin A1 induced activation of intracellular signaling molecules involved in PI3 K/AKT and MAPK signaling, and the proliferation-stimulating effect of ephrin A1 was mediated by activation of these pathways. Furthermore, ephrin A1 influenced expression and activation of various ER stress-related proteins and protected MAC-T cells from stress-induced cell death. Finally, ephrin A1 alleviated LPS-induced cell death through down-regulation of inflammatory cytokines. In conclusion, the results of this study suggest that the Eph A-ephrin A1 system is a positive factor in the increase and maintenance of epithelial cells in mammary glands of cows; the signaling system contributes to development, remodeling, and functionality of normal mammary glands and could overcome mastitis in cows and other mammals.
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Collections - Graduate School > Department of Biotechnology > 1. Journal Articles
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