Dataset Information

MiR-2478 inhibits TGF?1 expression by targeting the transcriptional activation region downstream of the TGF?1 promoter in dairy goats.

ABSTRACT: In a previous study, miR-2478 was demonstrated to be up-regulated in dairy goat mammary glands during peak lactation compared with the dry period. However, the detailed mechanisms by which miR-2478 regulates physiological lactation and mammary gland development in dairy goats remain unclear. In this study, we used bioinformatics analysis and homologous cloning to predict the target genes of miR-2478 and selected INSR, FBXO11, TGF?1 and ING4 as candidate target genes of miR-2478. Subsequently, by targeting the 5'UTR of the TGF?1 gene, we verified that miR-2478 significantly inhibited TGF?1 transcription and the Pearson's correlation coefficient between miR-2478 expression and TGF?1 expression was -0.98. Furthermore, we identified the potential promoter and transcription factor binding regions of TGF?1 and analyzed the potential mechanisms of interaction between miR-2478 and TGF?1. Dual-luciferase reporter assays revealed that two regions, spanning from -904 to -690?bp and from -79 to +197?bp, were transcription factor binding regions of TGF?1. Interesting, the miR-2478 binding sequence was determined to span from +123 to +142?bp in the TGF?1 gene promoter. Thus, our results have demonstrated that miR-2478 binds to the core region of the TGF?1 promoter and that it affects goat mammary gland development by inhibiting TGF?1 transcription.

SUBMITTER: Li Z

PROVIDER: S-EPMC5309801 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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miR-2478 inhibits TGFβ1 expression by targeting the transcriptional activation region downstream of the TGFβ1 promoter in dairy goats.

Li Zhuanjian Z Lan Xianyong X Han Ruili R Wang Jing J Huang Yongzhen Y Sun Jiajie J Guo Wenjiao W Chen Hong H

Scientific reports 20170215

In a previous study, miR-2478 was demonstrated to be up-regulated in dairy goat mammary glands during peak lactation compared with the dry period. However, the detailed mechanisms by which miR-2478 regulates physiological lactation and mammary gland development in dairy goats remain unclear. In this study, we used bioinformatics analysis and homologous cloning to predict the target genes of miR-2478 and selected INSR, FBXO11, TGFβ1 and ING4 as candidate target genes of miR-2478. Subsequently, by ...[more]

PMID: 28198456

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Project description:The high propensity of dietary polyunsaturated fatty acids (PUFA) to oxidation can induce a cascade of cellular immune-oxidative imbalances. On the other hand, PUFA, namely docosapentaenoic acid (ω6-DPA) and docosahexaenoic acid (DHA) can exert immunomodulatory effects by suppressing a pro-inflammatory response. Thus, the objective of this study was to investigate the effect of dietary supplementation with Schizochytrium spp. levels, rich in both ω6-DPA and DHA on the transcriptional profiling of genes involved in oxidative homeostasis and innate immunity of dairy goats' monocytes and neutrophils. Twenty-four dairy goats were divided into four homogeneous sub-groups; the diet of the control group (CON) had no Schizochytrium spp. while those of the treated groups were supplemented daily with 20 (ALG20), 40 (ALG40), and 60 (ALG60) g/goat/day. The mRNA levels of MGST1 in neutrophils were downregulated (p = 0.037), while in monocytes, SOD2 and SOD3 were downregulated (p = 0.010 and p = 0.044, respectively) in ALG60 compared to the CON group. GPX2 mRNA levels were downregulated (p = 0.036) in ALG20 and ALG60 compared to the CON group in neutrophils. NOX1 was upregulated (p = 0.043) in the neutrophiles of ALG60-goats. NOX2 was upregulated (p = 0.042) in the monocytes of ALG40-fed goats, while higher (p = 0.045) levels were also found in the ALG60 group in neutrophils. The mRNA levels of COX2 were downregulated (p = 0.035) in monocytes of the ALG40 and ALG60 groups. The mRNA levels of PTGER2 were also downregulated (p = 0.004) in monocytes of Schizochytrium-fed goats, while in neutrophils, significant downregulation (p = 0.024) was only found for ALG60 compared to the CON group. ALOX5AP mRNA levels were significantly decreased (p = 0.033) in ALG60 compared to the CON group in monocytes. LTA4H mRNA levels were increased (p = 0.015) in ALG60 compared to ALG20 and ALG40 groups in monocytes, while in neutrophils, a significant downregulation (p = 0.028) was observed in ALG20 compared to the CON group. The inclusion of more than 20 g Schizochytrium spp./day in goats' diet induced imbalances in mechanisms that regulate the antioxidant system, while downregulated the expression of pro-inflammatory pathways in monocytes and neutrophils.

Dataset Information

MiR-2478 inhibits TGF?1 expression by targeting the transcriptional activation region downstream of the TGF?1 promoter in dairy goats.

Publications

miR-2478 inhibits TGFβ1 expression by targeting the transcriptional activation region downstream of the TGFβ1 promoter in dairy goats.

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