Kisspeptin-10 Induces β-Casein Synthesis via GPR54 and Its Downstream Signaling Pathways in Bovine Mammary Epithelial Cells
Kisspeptin-10 Induces β-Casein Synthesis via GPR54 and Its Downstream Signaling Pathways in Bovine Mammary Epithelial Cells
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Kisspeptin-10 通过 GPR54 诱导牛乳腺上皮细胞中的 β-酪蛋白合成及其下游信号通路
DOI：
10.3390/ijms18122621
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发表时间：
2017-12
影响因子：
5.6
通讯作者：
Shoupeng Fu
中科院分区：
文献类型：
--
作者：
Jianhua Sun;Juxiong Liu;Bingxu Huang;Xingchi Kan;Guangxin Chen;Wei Wang;Shoupeng Fu
Kisspeptins（Kps）在调节GnRH轴中起关键作用，并通过与GPR 54结合而作为抗转移剂。最近，我们观察到GPR 54在优质乳奶牛的泌乳乳腺组织中的表达（乳蛋白产量为0.81 ± 0.13 kg/天;乳脂产量为1.07 ± 0.18 kg/天）高于低质乳奶牛（乳蛋白产量为0.51 ± 0.14 kg/天;乳脂产量为0.67 ± 0.22 kg/天）。我们推测Kp-10可能通过GPR 54及其下游信号调节乳蛋白β-酪蛋白（CSN 2）的合成。首先，我们从泌乳期荷斯坦奶牛中分离牛乳腺上皮细胞（bMEC），并用不同浓度的Kp-10处理它们。与对照细胞相比，在100 nM浓度的Kp-10下，CSN 2的合成显著增加。此外，当细胞用GPR 54肽-234（P-234）的选择性抑制剂预处理时，CSN 2合成的增加作用被阻断。Kp-10可激活bMEC中的ERK 1/2、AKT、mTOR和STAT 5。用U 0126、MK 2206、Rapamycin和AG 490抑制ERK 1/2、AKT、mTOR和STAT 5可阻断Kp-10的作用。总之，这些结果表明Kp-10通过GPR 54及其下游信号通路mTOR、ERK 1/2、STAT 5和AKT促进CSN 2的合成。
Kisspeptins (Kps) play a key role in the regulation of GnRH axis and as an anti-metastasis agent by binding with GPR54. Recently, we observed that the expression of GPR54 was higher in the lactating mammary tissues of dairy cows with high-quality milk (0.81 ± 0.13 kg/day of milk protein yield; 1.07 ± 0.18 kg/day of milk fat yield) than in those with low-quality milk (0.51 ± 0.14 kg/day of milk protein yield; 0.67 ± 0.22 kg/day of milk fat yield). We hypothesized that Kp-10 might regulate the milk protein, β-casein (CSN2) synthesis via GPR54 and its downstream signaling. First, we isolated the bovine mammary epithelial cells (bMECs) from lactating Holstein dairy cows, and treated them with different concentrations of Kp-10. Compared with the control cells, the synthesis of CSN2 is significantly increased at a concentration of 100 nM of Kp-10. In addition, the increased effect of CSN2 synthesis was blocked when the cells were pre-treated with the selective inhibitor of GPR54 Peptide-234 (P-234). Mechanistic study revealed that Kp-10 activated ERK1/2, AKT, mTOR and STAT5 in bMECs. Moreover, inhibiting ERK1/2, AKT, mTOR and STAT5 with U0126, MK2206, Rapamycin and AG490 could block the effects of Kp-10. Together, these results demonstrate that Kp-10 facilitates the synthesis of CSN2 via GPR54 and its downstream signaling pathways mTOR, ERK1/2, STAT5 and AKT.
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DOI：
10.1152/ajpendo.00426.2009
发表时间：
2010-02
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
Curtis AE;Cooke JH;Baxter JE;Parkinson JR;Bataveljic A;Ghatei MA;Bloom SR;Murphy KG
通讯作者：
Murphy KG
用于研究乳汁合成的泌乳牛乳腺上皮细胞模型的建立和表征
影响因子：
3.9
作者：
Zhao, Ke;Liu, Hong-Yun;Liu, Jian-Xin
通讯作者：
Liu, Jian-Xin
DOI：
10.1017/s1751731116000987
发表时间：
2016-05
期刊：
Animal : an international journal of animal bioscience
影响因子：
--
作者：
S. McCoard;A. Hayashi;Q. Sciascia;J. Rounce;B. Sinclair;W. McNabb;N. Roy
通讯作者：
S. McCoard;A. Hayashi;Q. Sciascia;J. Rounce;B. Sinclair;W. McNabb;N. Roy
影响因子：
4.8
作者：
Roa, J.;Garcia-Galiano, D.;Tena-Sempere, M.
通讯作者：
Tena-Sempere, M.
影响因子：
2.1
作者：
Selvaggi, Maria;D'Alessandro, Angela Gabriella;Dario, Cataldo
通讯作者：
Dario, Cataldo