Kp-10 promotes bovine mammary epithelial cell proliferation by activating GPR54 and its downstream signaling pathways

Kp-10 promotes bovine mammary epithelial cell proliferation by activating GPR54 and its downstream signaling pathways
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Kp-10通过激活GPR54及其下游信号通路促进牛乳腺上皮细胞增殖

DOI:
10.1002/jcp.29325
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发表时间:
2019-10-17
影响因子:
5.6
通讯作者:
Liu, Juxiong
Liu, Juxiong
中科院分区:
生物学2区
文献类型:
--
作者:
Li, Yanwei;Cao, Yu;Liu, Juxiong

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已有研究表明,乳腺上皮细胞的增殖和凋亡影响产奶量。因此,确保足够的乳腺上皮细胞有望提高产奶量。本研究旨在研究Kisspeptin-10(Kp-10)对牛乳腺上皮细胞(bMEC)增殖的影响,并探讨其作用机制。用不同浓度的Kp-10(1、10、100和1,000 nM)处理bMEC,100 nM Kp-10促进bMEC的增殖。Kp-10促进细胞周期从G1期向S期和G2期的转变,增加Cyclin D1和Cyclin D3的蛋白水平,并降低p21基因的表达水平。这项研究还表明,G蛋白偶联受体54(GPR 54),AKT,mTOR和ERK 1/2的抑制降低了Kp-10诱导的bMEC的增殖。此外,Kp-10降低Rb和E2 F1形成的复合物,并增加E2 F1靶基因的表达水平。这些结果表明,Kp-10通过激活GPR 54及其下游信号通路促进bMEC增殖。
It has been reported that the proliferation and apoptosis of mammary epithelial cells affect milk production. Therefore, ensuring adequate mammary epithelial cells is expected to enhance milk production. This study is devoted to studying the effects of kisspeptin‐10 (Kp‐10), a peptide hormone composed of 10 amino acids, on bovine mammary epithelial cell (bMEC) proliferation and exploring the underlying mechanism of its action. bMECs were treated with various concentrations of Kp‐10 (1, 10, 100, and 1,000 nM), and 100 nM Kp‐10 promoted the proliferation of the bMECs. Kp‐10 promoted the cell cycle transition from G1 to the S and G2 phases, increased the protein levels of Cyclin D1 and Cyclin D3, and reduced the expression levels of the p21 gene. This study also showed that inhibition of G protein‐coupled receptor 54 (GPR54), AKT, mTOR, and ERK1/2 reduced the proliferation of the bMECs that had been induced by Kp‐10. In addition, Kp‐10 decreased the complexes formed by Rb and E2F1 and increased the expression levels of the E2F1 target genes. These results indicate that Kp‐10 promotes bMEC proliferation by activating GPR54 and its downstream signaling pathways.