WISP3 (CCN6) Regulates Milk Protein Synthesis and Cell Growth Through mTOR Signaling in Dairy Cow Mammary Epithelial Cells

Jiang, Nan; Wang, Yu; Yu, Zhiqiang; Hu, Lijun; Liu, Chaonan; Gao, Xueli; Zheng, Shangen

doi:10.1089/dna.2015.2829

Cited by 16 publications

(12 citation statements)

References 76 publications

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“…In dairy cattle, it was suggested that WISP3 is an important regulatory factor involved in the amino acid‐mediated regulation of milk protein synthesis and mammary epithelial cell growth (Jiang et al . ). Sebag et al .…”

Section: Summary Statistics For Body Weight At Tagging (Bwt) and At 2mentioning

confidence: 97%

Bayesian genome‐wide association analysis for body weight in farmed Atlantic salmon (Salmo salar L.)

Yoshida

Lhorente²,

Carvalheiro

et al. 2017

Animal Genetics

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We performed a genome-wide association study to detect markers associated with growth traits in Atlantic salmon. The analyzed traits included body weight at tagging (BWT) and body weight at 25 months (BW25M). Genotypes of 4662 animals were imputed from the 50K SNP chip to the 200K SNP chip using fimpute software. The markers were simultaneously modeled using Bayes C to identify genomic regions associated with the traits. We identified windows explaining a maximum of 3.71% and 3.61% of the genetic variance for BWT and BW25M respectively. We found potential candidate genes located within the top ten 1-Mb windows for BWT and BW25M. For instance, the vitronectin (VTN) gene, which has been previously reported to be associated with cell growth, was found within one of the top ten 1-Mb windows for BWT. In addition, the WNT1-inducible-signaling pathway protein 3, melanocortin 2 receptor accessory protein 2, myosin light chain kinase, transforming growth factor beta receptor type 3 and myosin light chain 1 genes, which have been reported to be associated with skeletal growth in humans, growth stimulation during the larval stage in zebrafish, body weight in pigs, feed conversion in chickens and growth rate of sheep skeletal muscle respectively, were found within some of the top ten 1-Mb windows for BW25M. These results indicate that growth traits are most likely controlled by many variants with relatively small effects in Atlantic salmon. The genomic regions associated with the traits studied here may provide further insight into the functional regions underlying growth traits in this species.

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Section: Summary Statistics For Body Weight At Tagging (Bwt) and At 2mentioning

confidence: 97%

Bayesian genome‐wide association analysis for body weight in farmed Atlantic salmon (Salmo salar L.)

Yoshida

Lhorente²,

Carvalheiro

et al. 2017

Animal Genetics

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“…AA, particularly branched-chain AA, can participate in various cell physiological processes including cell growth, cell differentiation, cell metabolism, cell apoptosis and protein synthesis (Saxton and Sabatini, 2017). In DCMECs, AA are one of the most important regulatory factors for cell growth and lactation (Jiang et al ., 2015 a , 2015 b ). In this study, the cells were treated with different concentrations of AA, and the cell growth and casein synthesis were assessed.…”

Section: Discussionmentioning

confidence: 99%

“…The dairy cow mammary epithelial cells (DCMECs) were obtained from our lab (Jiang et al ., 2015 a , 2015 b ) and cultured with DMEM/F12 media (11320033, Gibco, California, USA) containing 10% fetal bovine serum (FBS, 16000044, Gibco) as previously report (Tong et al ., 2011). For the experiment, DCMECs were plated into 6 well plates with 1.0 × 10 5 cells per well and cultured with DMEM/F12 medium containing 10% FBS at 37 °C with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

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Septin6 regulates cell growth and casein synthesis in dairy cow mammary epithelial cells via mTORC1 pathway

Zhuzha

et al. 2019

Journal of Dairy Research

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This research paper addresses the hypothesis that Septin6 is a key regulatory factor influencing amino acid (AA)-mediated cell growth and casein synthesis in dairy cow mammary epithelial cells (DCMECs). DCMECs were treated with absence of AA (AA−), restricted concentrations of AA (AAr) or normal concentrations of AA (AA+) for 24 h. Cell growth, expression of CSN2 and Septin6 were increased in response to AA supply. Overexpressing or inhibiting Septin6 demonstrated that cell growth, expression of CSN2, mTOR, p-mTOR, S6K1 and p-S6K1 were up-regulated by Septin6. Furthermore, overexpressing or inhibiting mTOR demonstrated that the increase in cell growth and expression of CSN2 in response to Septin6 overexpression were inhibited by mTOR inhibition, and vice versa. Our hypothesis was supported; we were able to show that Septin6 is an important positive factor for cell growth and casein synthesis, it up-regulates AA-mediated cell growth and casein synthesis through activating mTORC1 pathway in DCMECs.

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“…At present, we have found that Kp-10 can promote CSN2 synthesis by activating GPR54.However, the exact molecular mechanism remains unclear, and so the next step is to detect the changes in downstream signals in the process. The CSN2 synthesis process is likely to include several participating signaling pathways, including ERK1/2, AKT, STAT, mTOR [ 6 , 19 , 20 , 40 , 41 ]. In addition, Kp-10 plays the role of an anti-metastasis agent via β-arrestin2/ERK by binding with GPR54 in human breast cancer cells [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Kisspeptin-10 Induces β-Casein Synthesis via GPR54 and Its Downstream Signaling Pathways in Bovine Mammary Epithelial Cells

Sun

Liu

Huang

et al. 2017

IJMS

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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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WISP3 (CCN6) Regulates Milk Protein Synthesis and Cell Growth Through mTOR Signaling in Dairy Cow Mammary Epithelial Cells

Cited by 16 publications

References 76 publications

Bayesian genome‐wide association analysis for body weight in farmed Atlantic salmon (Salmo salar L.)

Bayesian genome‐wide association analysis for body weight in farmed Atlantic salmon (Salmo salar L.)

Septin6 regulates cell growth and casein synthesis in dairy cow mammary epithelial cells via mTORC1 pathway

Kisspeptin-10 Induces β-Casein Synthesis via GPR54 and Its Downstream Signaling Pathways in Bovine Mammary Epithelial Cells

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