title: WISP3 (CCN6) Regulates Milk Protein Synthesis and Cell Growth Through mTOR Signaling in Dairy Cow Mammary Epithelial Cells.
abstract: The mTOR/S6K1 signaling pathway is the primary regulator of milk protein synthesis. While mTOR is known to be regulated at the translational level by amino acids, the mechanism by which mTOR accepts the amino acid signal is not yet clear. In this study, we describe the discovery of WISP3 as a potentially novel signaling factor that connects mTOR and amino acids. Treatment of dairy cow mammary epithelial cells with amino acids (lysine or methionine) increased both cell growth and the expression of β-casein (CSN2), WISP3, mTOR, and phospho-mTOR (p-mTOR). Notably, overexpressing WISP3 in these cells also increased both cell growth and the expression of CSN2, mTOR, and p-mTOR and decreased the expression of glycogen synthase kinase 3β (GSK3β), while repressing WISP3 had the opposite effect. The increase of the expression of CSN2, mTOR, and p-mTOR mediated by amino acid could be inhibited by repressing WISP3. The increase of the expression of CSN2, mTOR, and p-mTOR mediated by WISP3 overexpression could be inhibited by overexpressing GSK3β, and vice versa. Taken together, these results reveal that through its amino acid-mediated regulation of the mTOR pathway, WISP3 is an important regulatory factor involved in the amino acid-mediated regulation of milk protein synthesis and cell growth.
authors.affiliation: The Laboratory of Pathophysiology in College of Veterinary Medicine, Northeast Agricultural University , Harbin, People's Republic of China .
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: The Laboratory of Pathophysiology in College of Veterinary Medicine, Northeast Agricultural University , Harbin, People's Republic of China .
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Laboratory of Pathophysiology in College of Veterinary Medicine, Northeast Agricultural University , Harbin, People's Republic of China .
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: The Laboratory of Pathophysiology in College of Veterinary Medicine, Northeast Agricultural University , Harbin, People's Republic of China .
authors.forename: Lijun
authors.initials: L
authors.lastname: Hu
authors.affiliation: The Laboratory of Pathophysiology in College of Veterinary Medicine, Northeast Agricultural University , Harbin, People's Republic of China .
authors.forename: Chaonan
authors.initials: C
authors.lastname: Liu
authors.affiliation: The Laboratory of Pathophysiology in College of Veterinary Medicine, Northeast Agricultural University , Harbin, People's Republic of China .
authors.forename: Xueli
authors.initials: X
authors.lastname: Gao
authors.affiliation: The Laboratory of Pathophysiology in College of Veterinary Medicine, Northeast Agricultural University , Harbin, People's Republic of China .
authors.forename: Shimin
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics / Q000502:physiology*; D002417:Cattle; D049109:Cell Proliferation / Q000235:genetics*; D003612:Dairying; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D007774:Lactation / Q000502:physiology; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008894:Milk Proteins / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D055511:CCN Intercellular Signaling Proteins; D008894:Milk Proteins; D058570:TOR Serine-Threonine Kinases