title: AG and UAG induce β-casein expression via activation of ERK1/2 and AKT pathways.
abstract: 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.
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Sunan
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Juxiong
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Qingkang
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Endocrinology and MetabolismThe Second Hospital of Jilin University, Changchun, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Shiyao
authors.initials: S
authors.lastname: Xu
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Yang
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Bingxu
authors.initials: B
authors.lastname: Huang
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Yalong
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: College of Veterinary MedicineJilin University.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Veterinary MedicineJilin University wang_wei99@jlu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000215:Acylation; D000818:Animals; D002364:Caseins / Q000235:genetics*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D054439:Ghrelin / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002364:Caseins; D054439:Ghrelin; D054440:Receptors, Ghrelin; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: acylated ghrelin; bovine mammary epithelial cells; unacylated ghrelin; β-casein