AG and UAG induce β-casein expression via activation of ERK1/2 and AKT pathways.
AG and UAG induce β-casein expression via activation of ERK1/2 and AKT pathways.
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AG 和 UAG 通过激活 ERK1/2 和 AKT 途径诱导 β-酪蛋白表达
DOI：
10.1530/jme-15-0287
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发表时间：
2016-04
影响因子：
3.5
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Li S;Liu J;Lv Q;Zhang C;Xu S;Yang D;Huang B;Zeng Y;Gao Y;Wang W
发现胃饥饿素肽以两种主要形式循环：酰化胃饥饿素（AG）和未酰化胃饥饿素（UAG）。先前的研究表明，AG调节乳腺上皮细胞中β-酪蛋白（CSN 2）的表达。然而，AG调控CSN 2基因和蛋白表达的机制知之甚少。有证据表明，UAG通过GHSR 1a非依赖性机制具有生物活性。在这里，我们研究了可能的GHSR 1a介导的影响，UAG对CSN 2的表达在原代牛乳腺上皮细胞（pbMEC）从泌乳奶牛分离。我们发现，与对照组相比，AG和UAG均以剂量依赖性方式增加pbMEC中CSN 2的表达。[D-Lys 3]-GHRP-6（GHSR 1a的拮抗剂）和NF 449（Gs-α亚基抑制剂）可阻断pbMEC中CSN 2的表达。此外，AG和UAG均激活pbMEC中AKT/蛋白激酶B（AKT）和细胞外信号调节激酶1/2（ERK 1/2）通路，而[D-Lys 3]-GHRP-6和NF 449分别抑制pbMEC中AKT和ERK 1/2的磷酸化。阻断ERK 1/2和AKT信号通路可抑制AG或UAG诱导的CSN 2表达。最后，我们发现AG和UAG通过相同的信号通路引起细胞增殖。综上所述，这些结果表明AG和UAG均作用于ERK 1/2和AKT信号通路，以GHSR 1a依赖性方式促进CSN 2的表达。
The ghrelin peptides were found to circulate in two major forms: acylated ghrelin (AG) and unacylated ghrelin (UAG). Previous studies showed that AG regulates β-casein (CSN2) expression in mammary epithelial cells. However, little is known about the mechanisms by which AG regulates CSN2 gene and protein expression. Evidence suggests that UAG has biological activity through GHSR1a-independent mechanisms. Here, we investigated the possible GHSR1a-mediated effect of UAG on the expression of CSN2 in primary bovine mammary epithelial cells (pbMECs) isolated from lactating cow. We found that both AG and UAG increase the expression of CSN2 in a dose-dependent manner in pbMECs in comparison with the control group. Increased expression of CSN2 was blocked by [D-Lys3]-GHRP-6 (an antagonist of the GHSR1a) and NF449 (a Gs-α subunit inhibitor) in pbMECs. In addition, both AG and UAG activated AKT/protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways, whereas [D-Lys3]-GHRP-6 and NF449 inhibited the phosphorylation of AKT and ERK1/2 in pbMECs respectively. Blockade of ERK1/2 and AKT signaling pathways prevented the expression of CSN2 induced by AG or UAG. Finally, we found that both AG and UAG cause cell proliferation through identical signaling pathways. Taken together, these results demonstrate that both AG and UAG act on ERK1/2 and AKT signaling pathways to facilitate the expression of CSN2 in a GHSR1a-dependent manner.