Expression and Localization of Extracellular Matrix-Degrading Proteinases and Their Inhibitors in the Bovine Mammary Gland During Development, Function, and Involution

Rabot, Aline; Sinowatz, Fred; Berisha, Bajram; Meyer, Heiko; Schams, D.

doi:10.3168/jds.s0022-0302(07)71558-8

Cited by 39 publications

(42 citation statements)

References 31 publications

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“…At the same time, the disruption of cell junctions may initiate a cell unhooking process in the mammary epithelium, leading to a loss of cell communication with the extracellular matrix and neighboring cells, which is known to induce apoptosis (42). In ODM udder halves, the upregulation of genes such as MMP9 and TIMP2 (involved in the regulation of metalloprotease activity and degradation of the extracellular matrix) suggests mammary gland remodeling similar to that which occurs during mammary gland involution (44,59). Moreover, several transcripts belonging to the cellular assemblage and organization family and from the extracellular matrix were differentially expressed, such as COL1A1, KRT8, KRT5, KRT7, LUM, and MUC15.…”

Section: Discussionmentioning

confidence: 97%

Unilateral once daily milking locally induces differential gene expression in both mammary tissue and milk epithelial cells revealing mammary remodeling

Boutinaud

Galio²,

Lollivier

et al. 2013

Physiological Genomics

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Section: Discussionmentioning

confidence: 97%

Unilateral once daily milking locally induces differential gene expression in both mammary tissue and milk epithelial cells revealing mammary remodeling

Boutinaud

Galio²,

Lollivier

et al. 2013

Physiological Genomics

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“…Activation of the MMP system is involved in the remodeling of the extracellular matrix during mammary gland involution (Rabot et al, 2007;Tremblay et al, 2009;Ponchon et al, 2014). Increases in MMP2 and COL1A1 mRNA abundance in mammary tissue and in MMP2 and MMP9 activities in mammary secretions indicated a greater potential proteolysis of the mammary extracellular matrix components during the early phase of the dry period.…”

Section: Early Dry Period and Key Biomarkers Of Mammary Involutionmentioning

confidence: 99%

“…Remodeling of the mammary tissue is also linked with a destruction of the extracellular matrix. During mammary involution, the metalloproteinase (MMP) system is activated and induces the proteolysis of extracellular matrix components (Rabot et al, 2007;Tremblay et al, 2009). An example of extracellular matrix degradation biomarker is the increase in the MMP9 activity in milk analyzed by zymography (Tremblay et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

Boutinaud

Isaka

Gandemer

et al. 2017

Journal of Dairy Science

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The inhibition of prolactin release using cabergoline, a dopamine agonist, is an effective strategy to accelerate the changes in mammary secretion composition after drying-off. The objective of this study was to determine how cabergoline may affect mammary tissue remodeling during early involution. Holstein dairy cows were treated with either a single i.m. administration of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n = 7) or placebo (n = 7) at the time of drying-off. Mammary biopsy samples were collected 1 wk before drying-off (d −6), after 30 h of milk accumulation (d 1), and again 8 d following drying-off (d 8) to determine changes in gene expression, lactoferrin content, and cell turnover. Blood and mammary secretion samples were collected at d −6 and again at d 1, 2, 3, 4, 8, and 14 following the abrupt cessation of lactation to evaluate indicators of blood-milk barrier integrity and other markers of mammary tissue remodeling. Cabergoline induced less SLC2A1, BAX, CAPN2, and IGFBP5 mRNA expression. In contrast, cabergoline did not modify changes in cell proliferation and apoptosis. Following the cessation of lactation, changes in mammary secretion composition (Na + and K + ) and blood lactose concentrations were indicative of a loss in the blood-milk barrier function in both treatment groups. Cabergoline treatment affected only Na + and K + concentrations at d 1, suggesting a moderate increase in tight junction permeability. The increase in the activity of MMP9 and in mammary epithelial cell concentration in mammary secretions was greater in cabergoline-treated cows than in control cows, suggesting more mammary tissue remodeling. The increase in lactoferrin immunostaining in the mammary tissue occurred earlier for cabergoline-treated cows than for control cows, and was essentially localized in the stroma. Changes in some key markers of mammary involution suggest that cabergoline accelerates mammary gland remodeling. Thus, a single injection of cabergoline after the last milking would facilitate drying-off by enhancing mammary gland involution.

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“…Similarly in vivo, proteinases increase in the second phase of involution in the cow, which coincides with a concomitant expression of their inhibitors (Rabot et al 2007). Interestingly, although a population of bovine mammary epithelial cells undergo apoptosis initiated by milk stasis, neither sloughing of epithelial cells into the alveolar lumen nor detachment from the basement membrane occurs during the non-lactating period in the dairy cow (Sordillo & Nickerson 1988, Hurley Figure 6 Microarray analysis of milk protein gene expression in cow mammary explants.…”

Section: Discussionmentioning

confidence: 90%

Uncoupling the mechanisms that facilitate cell survival in hormone-deprived bovine mammary explants

Brennan

Sharp²,

Lefèvre³

et al. 2008

Journal of Molecular Endocrinology

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Mammary explants can be hormonally stimulated to mimic the biochemical changes that occur during lactogenesis. Previous studies using mammary explants concluded that the addition of exogenous macromolecules were required for mammary epithelial cells to remain viable in culture. The present study examines the survival of mammary explants from the dairy cow using milk protein gene expression as a functional marker of lactation and cell viability. Mammary explants cultured from late pregnant cows mimicked lactogenesis and showed significantly elevated milk protein gene expression after 3 days of culture with lactogenic hormones. The subsequent removal of exogenous hormones from the media for 10 days resulted in the down-regulation of milk protein genes. During this time, the mammary explants remained hormone responsive, the alveolar architecture was maintained and the expression of milk protein genes was re-induced after a second challenge with lactogenic hormones. We report that a population of bovine mammary epithelial cells have an intrinsic capacity to remain viable and hormone responsive for extended periods in chemically defined media without any exogenous macromolecules. In addition, we found mammary explant viability was dependent on de novo protein and RNA synthesis. Global functional microarray analysis showed that differential expression of genes involved in energy production, immune responses, oxidative stress and apoptosis signalling might contribute to cell survival. As the decline in milk production in dairy cattle after peak lactation results in considerable economic loss, the identification of novel survival genes may be used as genetic markers for breeding programmes to improve lactational persistency in dairy cows.

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Expression and Localization of Extracellular Matrix-Degrading Proteinases and Their Inhibitors in the Bovine Mammary Gland During Development, Function, and Involution

Cited by 39 publications

References 31 publications

Unilateral once daily milking locally induces differential gene expression in both mammary tissue and milk epithelial cells revealing mammary remodeling

Unilateral once daily milking locally induces differential gene expression in both mammary tissue and milk epithelial cells revealing mammary remodeling

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

Uncoupling the mechanisms that facilitate cell survival in hormone-deprived bovine mammary explants

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