title: SOCS3-mediated blockade reveals major contribution of JAK2/STAT5 signaling pathway to lactation and proliferation of dairy cow mammary epithelial cells in vitro.
abstract: Suppressor of cytokine signaling 3 (SOCS3) is a cytokine-induced negative feedback-loop regulator of cytokine signaling. More and more evidence has proved it to be an inhibitor of signal transducers and activators of transcription 5 (STAT5). Here, we used dairy cow mammary epithelial cells (DCMECs) to analyze the function of SOCS3 and the interaction between SOCS3 and STAT5a. The expression of SOCS3 was found in cytoplasm and nucleus of DCMECs by fluorescent immunostaining. Overexpression and inhibition of SOCS3 brought a remarkable milk protein synthesis change through the regulation of JAK2/STAT5a pathway activity, and SOCS3 expression also decreased SREBP-1c expression and fatty acid synthesis. Inhibited STAT5a activation correlated with reduced SOCS3 expression, which indicated that SOCS3 gene might be one of the targets of STAT5a activation, DCMECs treated with L-methionine (Met) resulted in a decrease of SOCS3 expression. SOCS3 could also decrease cell proliferation and viability by CASY-TT detection. Together, our findings indicate that SOCS3 acts as an inhibitor of JAK2/STAT5a pathway and disturbs fatty acid synthesis by decreasing SREBP-1c expression, which validates its involvement in both milk protein synthesis and fat synthesis. In aggregate, these results reveal that low SOCS3 expression is required for milk synthesis and proliferation of DCMECs in vitro.
authors.affiliation: Key laboratory of Dairy Science of Education Ministry, Northeast Agricultural University, Harbin 150030, Heilongjiang, China. gaoxj5390@sina.com.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.forename: Chao-Chao
authors.initials: CC
authors.lastname: Luo
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Si
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Qing-Zhang
authors.initials: QZ
authors.lastname: Li
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Gao
mesh_terms: D000818:Animals; D002364:Caseins / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D053614:Janus Kinase 2 / Q000378:metabolism*; D007774:Lactation / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D002364:Caseins; D005227:Fatty Acids; D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D053614:Janus Kinase 2; D058570:TOR Serine-Threonine Kinases