Expression of concern: MicroRNA-152 regulates DNA methyltransferase 1 and is involved in the development and lactation of Mammary Glands in Dairy Cows.
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ABSTRACT:
SUBMITTER: PLOS ONE Editors
PROVIDER: S-EPMC7323983 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Expression of concern: MicroRNA-152 regulates DNA methyltransferase 1 and is involved in the development and lactation of Mammary Glands in Dairy Cows.
PloS one 20200629 6
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Project description:MicroRNAs (miRNAs) are a class of small non-coding, endogenous regulatory RNAs that function by controlling gene expression at the post-transcriptional level. Using small RNA sequencing and qRT-PCR techniques, we found that the expression of miR-152 was significantly increased during lactation in the mammary glands of dairy cows producing high quality milk compared with that in cows producing low quality milk. Furthermore, DNA methyltransferase 1 (DNMT1), which is a target of miR-152, was inversely correlated with the expression levels of miR-152 in the mammary glands of dairy cows. Dairy cow mammary epithelial cells (DCMECs) were used as in vitro cell models to study the function of miR-152. The forced expression of miR-152 in DCMECs resulted in a marked reduction of DNMT1 at both mRNA and protein levels. This in turn led to a decrease in global DNA methylation and increased the expression of two lactation-related genes, serine/threonine protein kinase Akt (Akt) and peroxisome proliferator-activated receptor gamma (Pparγ). In contrast, inhibition of miR-152 showed the opposite results. By using an electronic Coulter counter (CASY-TT) and flow cytometer, we discovered that miR-152 enhanced the viability and multiplication capacity of DCMECs. In conclusion, miR-152 plays an important role in the development and lactation processes in the mammary glands of dairy cows. Our data provide insights into dairy cow mammary gland development and lactation.
| S-EPMC4079547 | biostudies-literature
Project description:Pten is a tumor suppressor gene regulating many cellular processes, including growth, adhesion, and apoptosis. In the aim of investigating the role of Pten during mammary gland development and lactation of dairy cows, we analyzed Pten expression levels in the mammary glands of dairy cows by using western blotting, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Dairy cow mammary epithelial cells (DCMECs) were used to study the function of Pten in vitro. We determined concentrations of β-casein, triglyceride, and lactose in the culture medium following Pten overexpression and siRNA inhibition. To determine whether Pten affected DCMEC viability and proliferation, cells were analyzed by CASY-TT and flow cytometry. Genes involved in lactation-related signaling pathways were detected. Pten expression was also assessed by adding prolactin and glucose to cell cultures. When Pten was overexpressed, proliferation of DCMECs and concentrations for β-casein, triglyceride, and lactose were significantly decreased. Overexpression of Pten down-regulated expression of MAPK, CYCLIN D1, AKT, MTOR, S6K1, STAT5, SREBP1, PPARγ, PRLR, and GLUT1, but up-regulated 4EBP1 in DCMECs. The Pten siRNA inhibition experiments revealed results that opposed those from the gene overexpression experiments. Introduction of prolactin (PRL) increased secretion of β-casein, triglyceride, and lactose, but decreased Pten expression levels. Introduction of glucose also increased β-casein and triglyceride concentrations, but did not significantly alter Pten expression levels. The Pten mRNA and protein expression levels were decreased 0.3- and 0.4-fold in mammary glands of lactating cows producing high quality milk (milk protein >3.0%, milk fat >3.5%), compared with those cows producing low quality milk (milk protein <3.0%, milk fat <3.5%). In conclusion, Pten functions as an inhibitor during mammary gland development and lactation in dairy cows. It can down-regulate DCMECs secretion of β-casein, triglyceride, and lactose, and plays a critical role in lactation related signaling pathways.
| S-EPMC4092105 | biostudies-literature
Project description:Epithelial barrier function in the mammary gland acts as a forefront of the defense mechanism against mastitis, which is widespread and a major disorder in dairy production. Chemerin is a chemoattractant protein with potent antimicrobial ability, but its role in the mammary gland remains unelucidated. The aim of this study was to determine the function of chemerin in mammary epithelial tissue of dairy cows in lactation or dry-off periods. Mammary epithelial cells produced chemerin protein, and secreted chemerin was detected in milk samples. Chemerin treatment promoted the proliferation of cultured bovine mammary epithelial cells and protected the integrity of the epithelial cell layer from hydrogen peroxide (H2O2)-induced damage. Meanwhile, chemerin levels were higher in mammary tissue with mastitis. Tumor necrosis factor alpha (TNF-α) strongly upregulated the expression of the chemerin-coding gene (RARRES2) in mammary epithelial cells. Therefore, chemerin was suggested to support mammary epithelial cell growth and epithelial barrier function and to be regulated by inflammatory stimuli. Our results may indicate chemerin as a novel therapeutic target for diseases in the bovine mammary gland.
| S-EPMC8614423 | biostudies-literature
Project description:Liver and mammary gland are among the most important organs during lactation in dairy cows. With the purpose of understanding both the different and the complementary roles and the crosstalk of those two organs during lactation, a transcriptome analysis was performed on liver and mammary tissues of 10 primiparous dairy cows in mid-lactation. The analysis was performed using a 4×44K Bovine Agilent microarray chip. The transcriptome difference between the two tissues was analyzed using SAS JMP Genomics using ANOVA with a false discovery rate correction (FDR). The analysis uncovered >9,000 genes differentially expressed (DEG) between the two tissues with a FDR<0.001. The functional analysis of the DEG uncovered a larger metabolic (especially related to lipid) and inflammatory response capacity in liver compared with mammary tissue while the mammary tissue had a larger protein synthesis and secretion, proliferation/differentiation, signaling, and innate immune system capacity compared with the liver. A plethora of endogenous compounds, cytokines, and transcription factors were estimated to control the DEG between the two tissues. Compared with mammary tissue, the liver transcriptome appeared to be under control of a large array of ligand-dependent nuclear receptors and, among endogenous chemical, fatty acids and bacteria-derived compounds. Compared with liver, the transcriptome of the mammary tissue was potentially under control of a large number of growth factors and miRNA. The in silico crosstalk analysis between the two tissues revealed an overall large communication with a reciprocal control of lipid metabolism, innate immune system adaptation, and proliferation/differentiation. In summary the transcriptome analysis confirmed prior known differences between liver and mammary tissue, especially considering the indication of a larger metabolic activity in liver compared with the mammary tissue and the larger protein synthesis, communication, and proliferative capacity in mammary tissue compared with the liver. Relatively novel is the indication by the data that the transcriptome of the liver is highly regulated by dietary and bacteria-related compounds while the mammary transcriptome is more under control of hormones, growth factors, and miRNA. A large crosstalk between the two tissues with a reciprocal control of metabolism and innate immune-adaptation was indicated by the network analysis that allowed uncovering previously unknown crosstalk between liver and mammary tissue for several signaling molecules.
| S-EPMC5349457 | biostudies-literature
Project description:BACKGROUND:Lactation is extremely important for dairy cows; however, the understanding of the underlying metabolic mechanisms is very limited. This study was conducted to investigate the inherent metabolic patterns during lactation using the overall biofluid metabolomics and the metabolic differences from non-lactation periods, as determined using partial tissue-metabolomics. We analyzed the metabolomic profiles of four biofluids (rumen fluid, serum, milk and urine) and their relationships in six mid-lactation Holstein cows and compared their mammary gland (MG) metabolomic profiles with those of six non-lactating cows by using gas chromatography-time of flight/mass spectrometry. RESULTS:In total, 33 metabolites were shared among the four biofluids, and 274 metabolites were identified in the MG tissues. The sub-clusters of the hierarchical clustering analysis revealed that the rumen fluid and serum metabolomics profiles were grouped together and highly correlated but were separate from those for milk. Urine had the most different profile compared to the other three biofluids. Creatine was identified as the most different metabolite among the four biofluids (VIP = 1.537). Five metabolic pathways, including gluconeogenesis, pyruvate metabolism, the tricarboxylic acid cycle (TCA cycle), glycerolipid metabolism, and aspartate metabolism, showed the most functional enrichment among the four biofluids (false discovery rate < 0.05, fold enrichment >2). Clear discriminations were observed in the MG metabolomics profiles between the lactating and non-lactating cows, with 54 metabolites having a significantly higher abundance (P < 0.05, VIP > 1) in the lactation group. Lactobionic acid, citric acid, orotic acid and oxamide were extracted by the S-plot as potential biomarkers of the metabolic difference between lactation and non-lactation. The TCA cycle, glyoxylate and dicarboxylate metabolism, glutamate metabolism and glycine metabolism were determined to be pathways that were significantly impacted (P < 0.01, impact value >0.1) in the lactation group. Among them, the TCA cycle was the most up-regulated pathway (P < 0.0001), with 7 of the 10 related metabolites increased in the MG tissues of the lactating cows. CONCLUSIONS:The overall biofluid and MG tissue metabolic mechanisms in the lactating cows were interpreted in this study. Our findings are the first to provide an integrated insight and a better understanding of the metabolic mechanism of lactation, which is beneficial for developing regulated strategies to improve the metabolic status of lactating dairy cows.
| S-EPMC5712200 | biostudies-literature
Project description:In recent years, studies related to the expression profiles of miRNAs in the dairy goat mammary gland were performed, but regulatory mechanisms in the physiological environment and the dynamic homeostasis of mammary gland development and lactation are not clear. In the present study, sequencing data analysis of early and late lactation uncovered a total of 1,487 unique miRNAs, including 45 novel miRNA candidates and 1,442 known and conserved miRNAs, of which 758 miRNAs were co-expressed and 378 differentially expressed with P < 0.05. Moreover, 76 non-redundant target genes were annotated in 347 GO consortiums, with 3,143 candidate target genes grouped into 33 pathways. Additionally, 18 predicted target genes of 214 miRNAs were directly annotated in mammary gland development and used to construct regulatory networks based on GO annotation and the KEGG pathway. The expression levels of seven known miRNAs and three novel miRNAs were examined using quantitative real-time PCR. The results showed that miRNAs might play important roles in early and late lactation during dairy goat mammary gland development, which will be helpful to obtain a better understanding of the genetic control of mammary gland lactation and development.
| S-EPMC5607250 | biostudies-literature
Project description:Our objective was to characterize the protein coding portion of the bovine mammary gland transcriptome by magnitude of RNA-seq read counts. EBseq analysis determined no differentially expressed genes due to postruminal lysine infusion, therefore, read counts were averaged across treatment and block. DAVID functional annotation analysis was utilized to determine specific gene ontologies and KEGG pathways to describe the data by magnitude of reads.
2021-03-19 | GSE148587 | GEO
Project description:This experiment was to evaluate the influence of sodium butyrate (SB) addition on milk production, ruminal fermentation, nutrient digestion, and the development and metabolism regulation of the mammary gland in dairy cows. Forty Holstein dairy cows averaging 710 ± 18.5 kg body weight, 72.8 ± 3.66 d in milk (DIM), and 41.4 ± 1.42 kg/d milk production were divided into four treatments blocked by DIM and milk production. Treatments were control group, low SB, medium SB, and high SB with 0, 100, 200 and 300 g/d of SB addition per cow, respectively. The study lasted for 105 d. Production of milk, milk protein and lactose quadratically increased (P < 0.05), while fat-corrected milk, energy-corrected milk and milk fat yields linearly increased (P < 0.05) with increasing SB addition. The digestibility of dietary dry matter, organic matter, and crude protein linearly increased (P < 0.05), whereas the digestibility of ether extract, neutral detergent fibre, and acid detergent fibre quadratically increased (P < 0.05). Ruminal pH quadratically decreased (P = 0.04), while total volatile fatty acids (VFA) quadratically increased (P = 0.03) with increasing SB addition. The acetic acid to propionic acid ratio increased (P = 0.03) linearly due to the unaltered acetic acid molar percentage and a linear decrease in propionic acid molar percentage. Ruminal enzymatic activity of carboxymethyl-cellulase and α-amylase, populations of total bacteria, total anaerobic fungi, total protozoa, Ruminococcus albus, R. flavefaciens, Butyrivibrio fibrisolvens, Fibrobacter succinogenes, and Ruminobacter amylophilus linearly increased (P < 0.05). Blood glucose, urea nitrogen, and non-esterified fatty acids linearly decreased (P < 0.05), while total protein concentration linearly increased (P = 0.04). Moreover, the addition of SB at 200 g/d promoted (P < 0.05) mRNA and protein expression of PPARγ, SREBF1, ACACA, FASN, SCD, CCNA2, CCND1, PCNA, Bcl-2, GPR41, and the ratios of p-Akt/Akt and p-mTOR/mTOR, but decreased (P < 0.05) mRNA and protein expressions of Bax, caspase-3, and caspase-9. The results suggest that milk production and milk fat synthesis increased with SB addition by stimulating rumen fermentation, nutrient digestion, gene and protein expressions concerned with milk fat synthesis and mammary gland development.
| S-EPMC10661553 | biostudies-literature
Project description:Hemorrhagic mastitis (HM) in dairy cows caused great economic losses in the dairy industry due to decreased milk production and increased costs associated with cattle management and treatment. However, the pathological and molecular mechanisms of HM are not well-understood. The present study aimed to investigate differentially expressed proteins (DEPs) associated with HM according to data-independent acquisition (DIA) proteomics. Compared to the mammary glands of healthylactating Holstein cows (Control, C group), the pathology of the HM group displayed massive alveolar infiltration of hemocytes and neutrophils, and the blood vessels, including arteriole, venules and capillaries were incomplete and damaged, with a loss of endothelial cells. DIA proteomics results showed that a total of 3,739 DEPs and 819 biological process terms were screened in the HM group. We focused on the blood, permeability of blood vessel, vascular and angiogenesis of mammary glands, and a total of 99 candidate DEPs, including 60 up- and 39 down-regulated DEPs, were obtained from the Gene Ontology (GO) and Pathway enrichment analyses. Phenotype prediction and function analysis of the DEPs revealed that three DEPs, particularly Caveolin-1(CAV1), were participated in the regulation of angiogenesis. Immunohistochemical and immunofluorescence staining showed that the CAV1 protein was present mainly in the mammary epithelial cells, vascular endothelial cells and vascular smooth muscle cells. The expression level of CAV1 mRNA and protein in the HM group was significantly down-regulated. The results will be helpful to the further understanding of the pathological and molecular mechanisms of HM in dairy cows.
| S-EPMC9393364 | biostudies-literature
Project description:BackgroundLong-term high-concentrate diet (HCD) feeding can cause subacute ruminal acidosis in cows and subsequently trigger systemic inflammatory and immune responses. Therefore, we conducted the present study in which twelve lactating cows installed with ruminal fistula were randomly assigned to the HCD group (forage:concentrate = 4:6, n = 6) or the low-concentrate diet (LCD) group (forage:concentrate = 6:4, n = 6) and were fed for 20 weeks. Ruminal fluid, plasma and mammary gland tissue samples were collected at week 20 for analysing lipopolysaccharide (LPS), pro-inflammatory cytokines, and immune relevant gene expression. The aim of this study was to investigate the effect of rumen-derived LPS on lingual antimicrobial peptide (LAP) synthesis and immune responses in mammary glands of lactating cows fed a HCD.ResultsCompared with the LCD group, the ruminal pH was lower in the HCD group, while LPS concentrations in the rumen, lacteal artery and vein were higher. The expression of LAP, BNBD5, IL-1β, IL-6, IL-8, and TNF-α was enhanced in the HCD group. LAP protein expression was higher in the HCD group than that in the LCD group. The expression of nuclear factor kappa B (NF-кB) did not change, but was activated, as the amounts of phosphorylated NF-kB and phosphorylated inhibitory kBα increased in the HCD group compared with that in the LCD group.ConclusionsAfter long-term HCD feeding, rumen-derived LPS translocated to the blood stream, triggered inflammatory and immune responses and enhanced LAP synthesis via the NF-kB signalling pathway in mammary glands of lactating cows.
| S-EPMC4924273 | biostudies-literature