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Food Deprivation Affects the miRNome in the Lactating Goat Mammary Gland.

Mobuchon L, Marthey S, Le Guillou S, Laloë D, Le Provost F, Leroux C - PLoS ONE (2015)

Bottom Line: Among the putative targets, 19 were previously identified as differently expressed genes (DEG).The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France; INRA, UMR1213 Herbivores, F-63122, Saint Genès Champanelle, France; Clermont Université, VetAgro Sup, UMR1213 Herbivores, BP 10448, F-63000, Clermont-Ferrand, France.

ABSTRACT

Background: Nutrition affects milk composition thus influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not fully understood. MicroRNAs (miRNA) are small non coding RNA which are important post-transcriptional regulators of gene expression by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, which may provide clues to deciphering regulations of the biosynthesis and secretion of milk components.

Methodology/principal findings: Using high-throughput sequencing technology, miRNomes of the lactating mammary gland were established from lactating goats fed ad libitum or deprived of food for 48 h affecting milk production and composition. High throughput miRNA sequencing revealed 30 miRNA with an expression potentially modulated by food deprivation; 16 were down-regulated and 14 were up-regulated. Diana-microT predictive tools suggested a potential role for several nutriregulated miRNA in lipid metabolism. Among the putative targets, 19 were previously identified as differently expressed genes (DEG). The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.

Conclusion/significance: In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland. Characterization of these 30 miRNA could contribute to a clearer understanding of gene regulation in the mammary gland in response to nutrition.

No MeSH data available.


Potential involvement of nutriregulated miRNA in milk fat synthesis.In red, miRNA which expression was up-regulated in FD goat mammary glands compared with Controls, while those whose expression was down-regulated are in blue.
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pone.0140111.g003: Potential involvement of nutriregulated miRNA in milk fat synthesis.In red, miRNA which expression was up-regulated in FD goat mammary glands compared with Controls, while those whose expression was down-regulated are in blue.

Mentions: Of all the 7,129 putative targets of nutriregulated miRNA, particular efforts were made to identify those involved in lipid metabolism. Very interestingly, nutriregulated miRNA may act in fatty acid availability (VLDLR), synthesis (ACACA), transport (FABP), activation (ACS) and desaturation (SCD), triglyceride synthesis (AGPAT) and in genes coding for proteins associated with the milk fat globule membrane (BTN, XDH) (Fig 3) [49]. Several nutriregulated miRNA also target transcription factors such as the SREBF1 and PPARγ cofactors, PPARGC1A and PPARGC1B that govern the expression of essential lipogenic enzymes in the mammary gland (Fig 3). Moreover, other genes related to milk lipid metabolism, such as INSIG2 (INSulin_Induced Genes 2) which codes for an endoplasmic reticulum protein that blocks the processing of SREBP, is predicted to be targeted by chr12_18027-5p [50]. Elsewhere, miR-204-5p may also target LPIN2 (LiPIN 2), recently characterized in the bovine mammary gland [49] and involved in triacylglycerol accumulation [51]. The gene coding for FADS1 (Fatty Acid DeSaturase 1), which plays a role in triacylglycerol synthesis [52], is potentially targeted by miR-671-5p. Furthermore, miR-125b-3p, miR-494-3p and chr3_3319-5p may conjointly target ABCA1 (ATP-Binding Cassette subfamily A member 1) which has been hypothesized to play a role in the transfer, storage and removal of cholesterol in the mammary gland [53]. Finally, five nutriregulated miRNA: miR-222-3p, miR-188-5p, miR-541-5p, miR-494-3p and chr3_3319-5p, may target PTEN (Phosphatase and TENsin homologue) (Fig 4). In particular, miR-494-3p binding has been confirmed experimentally in bronchial epithelial cells [54]. The role of PTEN has been characterized in dairy cow mammary epithelial cells (DCMECs), revealing that it plays a crucial role in the viability and proliferation capacity of cells, as well as in the secretion of β casein, triglycerides and lactose. In particular, PTEN may regulate the expression of key lactation-related pathways such as PPARγ, SREBF1, mTOR, PRLR and GLUT1, suggesting a pleiotropic role for PTEN in the lactation process [55].


Food Deprivation Affects the miRNome in the Lactating Goat Mammary Gland.

Mobuchon L, Marthey S, Le Guillou S, Laloë D, Le Provost F, Leroux C - PLoS ONE (2015)

Potential involvement of nutriregulated miRNA in milk fat synthesis.In red, miRNA which expression was up-regulated in FD goat mammary glands compared with Controls, while those whose expression was down-regulated are in blue.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608672&req=5

pone.0140111.g003: Potential involvement of nutriregulated miRNA in milk fat synthesis.In red, miRNA which expression was up-regulated in FD goat mammary glands compared with Controls, while those whose expression was down-regulated are in blue.
Mentions: Of all the 7,129 putative targets of nutriregulated miRNA, particular efforts were made to identify those involved in lipid metabolism. Very interestingly, nutriregulated miRNA may act in fatty acid availability (VLDLR), synthesis (ACACA), transport (FABP), activation (ACS) and desaturation (SCD), triglyceride synthesis (AGPAT) and in genes coding for proteins associated with the milk fat globule membrane (BTN, XDH) (Fig 3) [49]. Several nutriregulated miRNA also target transcription factors such as the SREBF1 and PPARγ cofactors, PPARGC1A and PPARGC1B that govern the expression of essential lipogenic enzymes in the mammary gland (Fig 3). Moreover, other genes related to milk lipid metabolism, such as INSIG2 (INSulin_Induced Genes 2) which codes for an endoplasmic reticulum protein that blocks the processing of SREBP, is predicted to be targeted by chr12_18027-5p [50]. Elsewhere, miR-204-5p may also target LPIN2 (LiPIN 2), recently characterized in the bovine mammary gland [49] and involved in triacylglycerol accumulation [51]. The gene coding for FADS1 (Fatty Acid DeSaturase 1), which plays a role in triacylglycerol synthesis [52], is potentially targeted by miR-671-5p. Furthermore, miR-125b-3p, miR-494-3p and chr3_3319-5p may conjointly target ABCA1 (ATP-Binding Cassette subfamily A member 1) which has been hypothesized to play a role in the transfer, storage and removal of cholesterol in the mammary gland [53]. Finally, five nutriregulated miRNA: miR-222-3p, miR-188-5p, miR-541-5p, miR-494-3p and chr3_3319-5p, may target PTEN (Phosphatase and TENsin homologue) (Fig 4). In particular, miR-494-3p binding has been confirmed experimentally in bronchial epithelial cells [54]. The role of PTEN has been characterized in dairy cow mammary epithelial cells (DCMECs), revealing that it plays a crucial role in the viability and proliferation capacity of cells, as well as in the secretion of β casein, triglycerides and lactose. In particular, PTEN may regulate the expression of key lactation-related pathways such as PPARγ, SREBF1, mTOR, PRLR and GLUT1, suggesting a pleiotropic role for PTEN in the lactation process [55].

Bottom Line: Among the putative targets, 19 were previously identified as differently expressed genes (DEG).The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France; INRA, UMR1213 Herbivores, F-63122, Saint Genès Champanelle, France; Clermont Université, VetAgro Sup, UMR1213 Herbivores, BP 10448, F-63000, Clermont-Ferrand, France.

ABSTRACT

Background: Nutrition affects milk composition thus influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not fully understood. MicroRNAs (miRNA) are small non coding RNA which are important post-transcriptional regulators of gene expression by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, which may provide clues to deciphering regulations of the biosynthesis and secretion of milk components.

Methodology/principal findings: Using high-throughput sequencing technology, miRNomes of the lactating mammary gland were established from lactating goats fed ad libitum or deprived of food for 48 h affecting milk production and composition. High throughput miRNA sequencing revealed 30 miRNA with an expression potentially modulated by food deprivation; 16 were down-regulated and 14 were up-regulated. Diana-microT predictive tools suggested a potential role for several nutriregulated miRNA in lipid metabolism. Among the putative targets, 19 were previously identified as differently expressed genes (DEG). The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.

Conclusion/significance: In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland. Characterization of these 30 miRNA could contribute to a clearer understanding of gene regulation in the mammary gland in response to nutrition.

No MeSH data available.