kisspeptin-10通过抑制SIRT6维持mTOR信号通路的激活以促进牛乳腺上皮细胞中乳蛋白的合成

Kisspeptin-10 Maintains the Activation of the mTOR Signaling Pathway by Inhibiting SIRT6 to Promote the Synthesis of Milk in Bovine Mammary Epithelial Cells.

作者信息

Cao Yu, Hu Guiqiu, Zhang Qing, Ma Lijun, Wang Jiaxin, Li Wen, Ge Yusong, Cheng Ji, Yang Zhanqing, Fu Shoupeng, Liu Juxiong

机构信息

College of Veterinary Medicine, Jilin University, Changchun 130062, China.

出版信息

J Agric Food Chem. 2021 Apr 14;69(14):4093-4100. doi: 10.1021/acs.jafc.0c07613. Epub 2021 Apr 5.

DOI:10.1021/acs.jafc.0c07613

Abstract

Kisspeptin-10 (Kp-10) is a peptide hormone that regulates normal physiological processes. The mechanism of Kp-10 in milk synthesis is still unclear. Therefore, bovine mammary epithelial cells (BMECs) were used to study the mechanism by which Kp-10 affects milk synthesis in BMECs. The GPR54 inhibitor and SIRT6 overexpression plasmid and siRNA were used to study the mechanism of regulating milk protein and milk fat synthesis by Kp-10. The results showed that 100 nM Kp-10 increased milk synthesis in BMECs. SIRT6 overexpression could significantly reduce the milk protein and milk fat synthesis in BMECs. Moreover, overexpression of SIRT6 reversed the activation of the Kp-10-induced mTOR signaling pathway. Further analysis suggested that SIRT6 might regulate the signal transduction of mTOR at the transcriptional level. These results strongly suggested that Kp-10/GPR54 activated the mTOR signaling pathway by inhibiting SIRT6 expression and then increased the milk synthesis in BMECs.

摘要

kisspeptin-10（Kp-10）是一种调节正常生理过程的肽类激素。Kp-10在乳汁合成中的作用机制尚不清楚。因此，本研究利用牛乳腺上皮细胞（BMECs）来探究Kp-10影响BMECs乳汁合成的机制。采用GPR54抑制剂、SIRT6过表达质粒和siRNA来研究Kp-10调控乳蛋白和乳脂肪合成的机制。结果显示，100 nM Kp-10可增加BMECs的乳汁合成。SIRT6过表达可显著降低BMECs的乳蛋白和乳脂肪合成。此外，SIRT6过表达可逆转Kp-10诱导的mTOR信号通路的激活。进一步分析表明，SIRT6可能在转录水平调节mTOR的信号转导。这些结果有力地表明，Kp-10/GPR54通过抑制SIRT6表达激活mTOR信号通路，进而增加BMECs的乳汁合成。