Isoflavones and their metabolites influence the milk component synthesis ability of mammary epithelial cells through prolactin/STAT5 signaling

Tsugami, Yusaku; Matsunaga, Kota; Suzuki, Takahiro; Nishimura, Takanori; Kobayashi, Ken

doi:10.1002/mnfr.201700156

Cited by 21 publications

(49 citation statements)

References 51 publications

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“…Soybean isoflavones are kinds of flavonoids existing in legume plants (Tsugami et al 2017). In recent years, some studies suggest that SI has played important roles in the treatment of human diseases, such as anti-tumor, anti-inflammatory, and anti-oxidative stress (Mortensen et al 2009;Russo et al 2016;Teixeira et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Proteomics study on the protective mechanism of soybean isoflavone against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae

Niu

Zhang

et al. 2021

Cell Stress and Chaperones

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This study aimed to verify the anti-inflammatory effect of soybean isoflavones (SI) on the inflammatory response induced by Streptococcus agalactiae (S. agalactiae) of bovine mammary epithelial cells (bMECs) and to elucidate its possible mechanism. BMECs were pretreated with SI of different concentrations (20, 40, 60, 80, 100 μg/mL) for 0.5, 3, 6, 9, 12, 15, 18, 24 h. And then, S. agalactiae was used to infect bMECs for 6 h (MOI = 50:1) to establish the inflammation model. Cell viability, growth curves of S. agalactiae, cytotoxicity, and S. agalactiae invasion rate were determined. A proteomics technique was used to further detect differential proteins and enrichment pathways. SI (40 μg/mL) improved the viability of bMECs at 12 h (p < 0.05) and 60 and 80 μg/mL of SI greater (p < 0.01). Moreover, 60 μg/mL of SI protects cells from bacterial damage (p < 0.05). SI could inhibit S. agalactiae growth and internalization into bMECs in a time-and dose-dependent manner. In addition, proteomics results showed that 133 proteins were up-regulated and 89 proteins were down-regulated significantly. The differentially significantly expressed proteins (DSEPs) were mainly related to cell proliferation, differentiation, apoptosis, and migration. GO annotation showed that 222 DSEPs were divided into 23 biological processes (BP) terms, 14 cell components (CC) terms, and 12 molecular functions (MF) terms. DSEPs were significantly enriched in 10 pathways, of which the immune pathway was the main enrichment pathway.

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Section: Introductionmentioning

confidence: 99%

Proteomics study on the protective mechanism of soybean isoflavone against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae

Niu

Zhang

et al. 2021

Cell Stress and Chaperones

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“…HC11 cells were cultured using RPMI 1640 medium containing 10% FBS, 5 μg/ml insulin (Sobarbio), 10 ng/ml epidermal growth factor (EGF, Sigma), 1 μg/ml dexamethasone (Sobarbio), and 1 μg/ml prolactin (Sigma) for 2 days. Subsequently, the cells (1 × 10 5 cells/ml) were seeded in 96‐well plates and administered various concentrations of the sample for 48 hr in RPMI 1640 medium with 10% FBS, 5 μg/ml insulin, 10 ng/ml EGF, 1 μg/ml dexamethasone, and 1 μg/ml prolactin (Tsugami, Matsunaga, Suzuki, Nishimura, & Kobayashi, 2017). The MTT method was used to evaluate the growth rate of the HC11 cells.…”

Section: Methodsmentioning

confidence: 99%

“…into the nucleus to mediate the transcription of genes correlated with casein synthesis (Tsugami et al, 2017). In addition, activated mTOR regulates the phosphorylation of S6K1 and 4EBP1 which induces milk protein translation during lactogenic differentiation (Galbaugh, Cerrito, Jose, & Cutler, 2006).…”

Section: The Active Peptides Increased the Expression Of Jak2-stat5mentioning

confidence: 99%

Identification of octopus peptide and its promotion of β‐casein synthesis in a mouse mammary epithelial cell line

et al. 2020

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Octopus protein hydrolysate has been reported to increase milk yield and milk protein production. In this paper, the utilization and underlying mechanisms of bioactive peptide fractions from octopus protein hydrolysate on β-casein expression in mouse mammary epithelial cells (HC11) were investigated. Fraction OPH3-1 significantly stimulated cell proliferation and β-casein synthesis in HC11 cells, which was purified by ultra-filtration and gel-filtration chromatography. The MWs of the peptides from OPH3-1 ranged from 525-2,578 Da and consisted of 7-26 amino acid residues. Most of the peptides demonstrated the typical characteristics of milk protein synthesis promotion, especially MGLAGPR, MGDVLNF, EAPLMHV, and TEAPLMHV. Additionally, the mRNA abundances of mTOR, S6K1, 4EBP1, JAK2, and STAT5 were significantly enhanced by OPH3-1, which was consistent with the increased β-casein expression. These results suggest that the OPH3-1 peptides can promote the proliferation of mammary epithelial cells and increase β-casein synthesis. Practical applications Breastfeeding mothers are generally recommended to take octopus soup as a daily diet to promote lactation. The peptides fraction OPH3-1 from the enzymatic hydrolysate of Octopus vulgaris which was revealed to significantly stimulate mammary epithelial cell proliferation and β-casein synthesis was obtained. This study suggests that octopus peptides can be used as nutritional supplements to increase the quantity and quality of milk production.

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“…Recently, we have reported that each isoflavone individually influences the milk production ability of MECs through prolactin/STAT5 signaling in different manners by using in vitro culture models of lactation. [ 12 ] Each isoflavone also shows different effects on the expression patterns of tight junction (TJ) proteins and the barrier functions of TJs in lactating MECs. [ 13 ] The mammary gland requires sufficient cell growth for ductal branching and alveolar formation during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

“…[ 21,22 ] We have previously reported that coumestrol, daidzein, and genistein directly influence the milk production ability of lactating MECs in different manners using a 2D cell culture model in vitro. [ 12 ] In this study, we prepared 3D cell culture models to induce ductal branching and alveolar structure formation to investigate the direct effects of each isoflavone on mammary morphogenesis in vitro. The direct effects of isoflavone on future milk production ability of MECs were also investigated using in vitro culture models of lactation.…”

Section: Introductionmentioning

confidence: 99%

Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells

et al. 2020

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Isoflavones are a class of flavonoids present in legumes and are called phytoestrogens because of their estrogen‐like activity. Endogenous estrogen is well known to regulate mammary gland morphogenesis during pregnancy. Each isoflavone also has different physiological activities. However, it is difficult to investigate the direct effect of each isoflavone in mammary morphogenesis in vivo because isoflavones are metabolized into different isoflavones by enteric bacteria. In this study, investigated are the direct influences of coumestrol, daidzein, and genistein on mammary structure development and future milk production ability of mammary epithelial cells (MECs) using in vitro culture models. Mouse MECs are cultured in Matrigel with basic fibroblast growth factor and epidermal growth factor to induce ductal branching and alveolar formation, respectively. Coumestrol and genistein inhibit ductal branching and alveolar formation by affecting the proliferation and migration of MECs with the induction of apoptosis. Daidzein hardly influences mammary structure development. Furthermore, pretreatment with coumestrol adversely affects the induction of milk production ability of MECs. These results suggest that each isoflavone differentially influences mammary morphogenesis and future milk production by affecting MEC behaviors. These results also suggest that the culture models are effective to study mammary epithelial morphogenesis in vitro.

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Isoflavones and their metabolites influence the milk component synthesis ability of mammary epithelial cells through prolactin/STAT5 signaling

Abstract: Isoflavones and their metabolites influence the milk production ability of MECs through different interactions with prolactin/STAT5 signaling. Simultaneous intake of multiple isoflavones by consumption of legumes may induce promotive or adverse effects on lactating MECs.

Cited by 21 publications

References 51 publications

Proteomics study on the protective mechanism of soybean isoflavone against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae

Proteomics study on the protective mechanism of soybean isoflavone against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae

Identification of octopus peptide and its promotion of β‐casein synthesis in a mouse mammary epithelial cell line

Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells

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