Epidermal Growth Factor Stimulates Fatty Acid Synthesis Mainly via PLC-γ1/Akt Signaling Pathway in Dairy Goat Mammary Epithelial Cells

Huang, Jun; Dai, Bangguo; Qu, Hexuan; Zhong, Yuan; Ma, Yue; Luo, Jun; Hadsell, Darryl L.; Shi, Huaiping

doi:10.3390/ani10060930

Cited by 8 publications

(7 citation statements)

References 53 publications

(53 reference statements)

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“…Several genes have been reported to be involved in ruminant milk fat synthesis, including EGFR, ACSS2, ACSL4, PANK3, DGAT2, and SP1. Among these, EGFR plays an important role in the de novo synthesis of fatty acids in mammary epithelial cells by phosphorylating PLC-γ1 and Akt signaling pathways, inducing adipogenesis-related gene expression and increasing intracellular TG content (Huang et al, 2020). ACSS2 (acyl-CoA synthase short-chain family member 2) performs lipogenesis by synthesizing acetyl-CoA from acetate, which is directly regulated by SREBP1 and plays an important role in ruminant milk fat synthesis (Mu et al, 2021).…”

Section: Candidate Genes Associated With Milk Fatmentioning

confidence: 99%

Whole-genome resequencing reveals genetic diversity and selection characteristics of dairy goat

Xiong

Bao

et al. 2023

Front. Genet.

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The dairy goat is one of the earliest dairy livestock species, which plays an important role in the economic development, especially for developing countries. With the development of agricultural civilization, dairy goats have been widely distributed across the world. However, few studies have been conducted on the specific characteristics of dairy goat. In this study, we collected the whole-genome data of 89 goat individuals by sequencing 48 goats and employing 41 publicly available goats, including five dairy goat breeds (Saanen, Nubian, Alpine, Toggenburg, and Guanzhong dairy goat; n = 24, 15, 11, 6, 6), and three goat breeds (Guishan goat, Longlin goat, Yunshang Black goat; n = 6, 15, 6). Through compared the genomes of dairy goat and non-dairy goat to analyze genetic diversity and selection characteristics of dairy goat. The results show that the eight goats could be divided into three subgroups of European, African, and Chinese indigenous goat populations, and we also found that Australian Nubian, Toggenburg, and Australian Alpine had the highest linkage disequilibrium, the lowest level of nucleotide diversity, and a higher inbreeding coefficient, indicating that they were strongly artificially selected. In addition, we identified several candidate genes related to the specificity of dairy goat, particularly genes associated with milk production traits (GHR, DGAT2, ELF5, GLYCAM1, ACSBG2, ACSS2), reproduction traits (TSHR, TSHB, PTGS2, ESR2), immunity traits (JAK1, POU2F2, LRRC66). Our results provide not only insights into the evolutionary history and breed characteristics of dairy goat, but also valuable information for the implementation and improvement of dairy goat cross breeding program.

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Section: Candidate Genes Associated With Milk Fatmentioning

confidence: 99%

Whole-genome resequencing reveals genetic diversity and selection characteristics of dairy goat

Xiong

Bao

et al. 2023

Front. Genet.

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“…This indicates that ELOVL6 not only regulates the elongation of fatty acid chains but also plays an active role in the de novo synthesis of FA and TAG. EGFR has a positive regulatory effect on the de novo synthesis of FA in goat mammary epithelial cells (FASN and ACACA), which is mainly mediated by the AKT and PLC-γ-1 signaling pathways [32]. Therefore, after interfering with the PI4K2A gene, the expression of ELOVL6 and EGFR were downregulated, indicates that PI4K2A may indirectly inhibit the synthesis of milk fat in cows.…”

Section: Discussionmentioning

confidence: 99%

The PI4K2A positively regulates the synthesis of milk fat in cows, promotes the proliferation of bovine mammary epithelial cells, and inhibits their apoptosis

Mu,

Hu,

Feng

et al. 2023

Preprint

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Background: Milk fat is the most important and energy-rich substance in milk. It is crucial to study the theory and pathways of milk fat synthesis and its regulation in dairy cows for the study of lactation biology. However, the current identification of valuable candidate genes affecting milk fat is limited. Method: This study uses real-time quantitative PCR (qRT-PCR) technology to perform tissue expression profile analysis on 15 candidate differentially expressed genes related to milk fat metabolism obtained from our previous transcriptome sequencing and weighted gene co-expression network analysis (WGCNA), to determine the key candidate genes affecting milk fat synthesis in dairy cows. Investigate the specific regulatory mechanisms of key candidate genes in cow milk fat metabolism using overexpression (adenovirus) and interference techniques (lentivirus). Results: The results showed that the expression level of PI4K2A gene in milk gland tissue was significantly higher than that in small intestine, liver, kidney, heart, and ovary (P < 0.05). Compared with other genes, the expression of PI4K2A in mammary gland tissue and bovine mammary epithelial cells (BMECs) was also higher and more stable. Ultimately, we identified PI4K2A as the key candidate gene responsible for regulating milk fat synthesis in dairy cows, and it plays a vital role in the cytoplasm of BMECs. Afterwards, we constructed the adenovirus overexpression vector and lentivirus interference vector for the PI4K2A gene, and combined quantitative real-time PCR (qRT-PCR) and western blot (WB) techniques to detect the effects of overexpressing and interfering with the PI4K2A gene on lipid metabolism in BMEC. The results indicate that the PI4K2A gene plays a positive regulatory role in the fatty acid (FA) transport process involved in milk fat synthesis in cows (P < 0.05). Upon further examination of triglycerides (TAG), cholesterol, and lipid droplet content in BMECs, we found that PI4K2A also has a positive regulatory effect on bovine milk fat synthesis (P < 0.05). The results obtained from EdU and apoptosis kit detection indicated that the PI4K2A gene positively regulated BMECs proliferation (P < 0.05) while negatively regulating their apoptosis process (P < 0.05). Conclusions: This study offers valuable genetic marker information for precise molecular breeding of milk component traits in dairy cows, with potential implications for mammary gland wound healing and treatment of mammary gland-related diseases.

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“…Studies have found that EGFR promotes adhesion between mammary gland cells and regulates the growth and differentiation of human mammary epithelial cells ( Mukhopadhyay et al, 2013 ). EGFR , at concentrations ranging from 12.5 to 50 ng/ml, facilitates the proliferation of mammary epithelial cells in dairy goats, and activation of the EGFR-mediated signaling pathway promotes the survival of mammary epithelial cells in dairy goats ( Huang et al, 2020 ). Therefore, the data obtained in this study provide a basis for future studies on the role of m 6 A methylation in the development of mammary glands in dairy goats.…”

Section: Discussionmentioning

confidence: 99%

Identification and functional analysis of m6A in the mammary gland tissues of dairy goats at the early and peak lactation stages

Wang

Zhang

Xuan

et al. 2022

Front. Cell Dev. Biol.

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N6-methyladenosine (m6A) is the most common reversible epigenetic RNA modification in the mRNA of all higher eukaryotic organisms and plays an important role in the regulation of gene expression and cell function. In this study, m6A-modified methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were used to identify the key genes with m6A modification during mammary gland development and lactation in dairy goats. The results showed that m6A methylation occurred at 3,927 loci, which were significantly enriched in the 3′ untranslated region (3′UTR) and the termination codon region. In the early stage and peak stage of lactation, m6A methylation occurred extensively in mammary tissues, and a total of 725 differentially expressed m6A-modified genes were obtained, all negatively correlated with mRNA expression. In addition, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that different methylated genes were mainly involved in the growth and apoptosis of mammary epithelial cells through signaling pathways, such as the mitogen-activated protein kinase (MAPK) and phospholipase D pathways, and then affected the development and lactation of mammary gland. All in all, we identified and analyzed the methylation events related to the development and lactation regulation of mammary gland at the early and peak lactation stages, and provided a theoretical basis to reveal the physiological regulatory system of mammary gland development and lactation in dairy goats.

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Epidermal Growth Factor Stimulates Fatty Acid Synthesis Mainly via PLC-γ1/Akt Signaling Pathway in Dairy Goat Mammary Epithelial Cells

Cited by 8 publications

References 53 publications

Whole-genome resequencing reveals genetic diversity and selection characteristics of dairy goat

Whole-genome resequencing reveals genetic diversity and selection characteristics of dairy goat

The PI4K2A positively regulates the synthesis of milk fat in cows, promotes the proliferation of bovine mammary epithelial cells, and inhibits their apoptosis

Identification and functional analysis of m6A in the mammary gland tissues of dairy goats at the early and peak lactation stages

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