Effect of Transforming Growth Factor-beta (TGF-β) on Mammary Development

Plaut, Karen; Dean, A.; Patnode, T. A.; Casey, Theresa

doi:10.3168/jds.s0022-0302(03)74036-3

Cited by 12 publications

(13 citation statements)

References 63 publications

(50 reference statements)

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“…Although staining intensity was not directly quantified in this study, we observed stronger intensity for TGF-β1 and TGF-βR2 in the epithelial compartment than in the stromal compartment. Localization of TGF-βR2 was consistent with previous literature that reported TGF-βR2 staining along the alveolar and ductal epithelium of heifers (Plaut et al, 2003).…”

Section: Discussionsupporting

confidence: 91%

“…It is also interesting to speculate that the greater number of fibroblasts observed at 1 WD may be due to increased abundance of TGF-β1 in the intralobular stroma at LL. The TGF-β1 protein in late lactation may be in latent form, which is activated by proteases at dry-off (reviewed by Plaut et al, 2003). Activated TGF-β1 may then stimulate proliferation of fibroblasts during involution.…”

Section: Discussionmentioning

confidence: 99%

“…Transforming growth factor-β1 (TGF-β1), a cytokine that acts through its type I and type II receptors (TGFβR2), is expressed in the bovine mammary gland during times of active remodeling and mediates stromal cell proliferation and epithelial cell apoptosis (for review, see Plaut et al, 2003). The greatest expression of TGF-β1 in the bovine mammary gland was detected during mammogenesis in prepubertal heifers and during early involution (Plath et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of mammary stromal remodeling during the dry period

Vries

Dover

Casey

et al. 2010

Journal of Dairy Science

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During the dry period between successive lactations, the mammary gland of dairy cows undergoes extensive remodeling that is marked by phases of involution and mammogenesis. Changes in the mammary epithelium during the dry period have been well characterized; however, few studies have examined the changes that occur in stromal tissue. The objective of this study was to characterize changes that occur in mammary stroma during the dry period. Mammary biopsies were taken from 9 multigravid Holstein cows in late lactation, at 1 wk after dry-off, 3 wk before expected calving date, and 1 wk before expected calving date. Tissue was fixed in formalin, embedded in paraffin, and cut into 5-mum sections. Sections were stained with hematoxylin and eosin or with immunohistochemistry for expression of smooth muscle alpha actin (SMA), fibronectin, stromelysin-1 (MMP-3), transforming growth factor-beta1 (TGF-beta1), and TGF-beta receptor 2 (TGF-betaR2). Images of tissues were captured with light microscopy, and imaging software was used to measure intralobular stromal area, number of activated fibroblasts, as identified by expression of SMA, and percentage of intralobular stromal area expressing fibronectin, MMP3, TGF-beta1, and TGF-betaR2. Analyses of variance were conducted and statistical differences were based on the least squares means of biopsy stage. Number of activated fibroblasts was greater at 1 wk dry than at 1 wk before calving (2,720 vs. 1,800 cells/mm(2)), percentage intralobular stromal area was greater at 1 wk dry (32%) and 3 wk before calving (37%) than at 1 wk before calving (25%), and TGF-beta1 expression decreased 15% from late lactation to the dry period. The percentages of stromal area expressing fibronectin, MMP-3, and TGF-betaR2 and the percentage of myofibroblasts were not different across biopsy stages. These results support the concept that stromal expression of transforming growth factor-beta1 and fibroblast proliferation may be important for remodeling during the dry period.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of mammary stromal remodeling during the dry period

Vries

Dover

Casey

et al. 2010

Journal of Dairy Science

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“…On the other hand, the transforming growth factor (TGF)-β is a well-known cytokine with its effect on cell growth and differentiation. TGF-β has 3 known isoforms in mammals; TGF-β1, TGF-β2, and TGF-β3 [22]. It has been reported that only TGF-β1 and TGF-β2 were detected in bovine milk [8,12].…”

Section: Introductionmentioning

confidence: 99%

Changes in Somatic Cell Count, Composition and Cytokine Levels in Milk from Cows with Mastitis Due to Mixed Infections

Safak

Rişvanlı

2021

Acta Scientiae. Vet.

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Background: Mastitis is a mammary gland inflammation that is very common worldwide, mostly caused by bacteria, and causes enormous economic losses. Many microorganisms cause this disease. The most common causes of mastitis by these microorganisms are Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Streptococcus agalactiae (S. agalactiae). The anti-inflammatory properties of transforming growth factor (TGF)-β include: 1) limiting interferon (IFN)-γ production; 2) increasing the expression of the ınterleukine (IL)-1 receptor antagonist; 3) inhibiting macrophage production of chemokines, pro-inflammatory cytokines, nitric oxide, and reactive oxygen intermediates; and 4) increasing macrophage clearance of bacterial debris and damaged parenchymal cells. It is stated that cytokines and milk composition change in case of mastitis. In this study, it was aimed to reveal the changes in milk TGF-β1 and Tumor necrosis factor (TNF)-α concentrations and milk composition in mixed infections caused by three pathogens causing mastitis.Materials, Methods & Results: In this study, milk samples from 90 cows were divided into 5 groups. Tumor necrosis factor (TNF)-α and TGF-β1 concentrations and milk composition were determined in these milk samples. The California Mastitis Test (CMT) was applied to the cows included in the study and scoring was done. According to the CMT results of the milk samples taken, CMT(-) cows were included in group 1 (n = 22). Those with the CMT(+) were taken to the microbiology laboratory for analysis within 2 h. After the bacteria was determined, combination groupings were formed. Group 2 (n = 17) with S. aureus and E. coli, group 3 (n = 21), S. agalactiae with S. aureus, S. agalactiae and E. coli together, group 4 (n = 8) and CMT (+) but no bacterial growth formed group 5 (n = 22).Somatic cell counts were made in the milk samples taken from the cows belonging to the groupings. Somatic cell count was measured with the DeLaval Cell Counter® (Cell Counter DCC) device. Mineral matter, fat, protein, lactose, electrical conductivity and specific gravity were measured in milk samples using Lactoscan Milk Analyzer (Milkotronic/EUROPE). Milk samples were then stored at -80°C to measure TGF-β1 and TNF-α. Tumor necrosis factor-α and TGF-β1 concentrations in milk samples were measured using ELISA kits (Sunred Biological Technology).Discussion: Changes in milk TNF-α and TGF-β1 concentration and milk composition were determined in milk samples with mastitis caused by mixed infection. The TNF-α concentration of group 4 was higher than the other groups. On the other hand, the highest concentration of TGF-β1 was found in group 2. While the number of somatic cells in group 1 was lower than in groups 2, 3, and 4, there was no statistical difference between groups 1 and 5. The lowest milk fat ratio was found in group 1, and it was found to be statistically lower than groups 2, 3, and 4. While the rate of solid-non-fat of group 1 increased compared to groups 2 and 3, the highest protein ratio was found in groups 1 and 5. There was no difference between the 5 groups in terms of mineral matter ratios. While the specific gravity was highest in group 1, there was no statistical difference between the other 4 groups. Overall, it was concluded that there was an increase in TNF-α and TGF-β1 concentrations and a change in milk composition in samples with bacterial growth.Keywords: bovine mastitis, cytokine, milk composition, raw milk, transforming growth factor.

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“…Transforming growth factor-betas (TGF-β) comprise a super-family of proteins that includes TGF-β1, β2, and β3 as well as activins and inhibins (Kingsley, 1994). Transforming growth factor-β1 regulates mammary development, and its expression is greatest during periods of tissue remodeling (for review, see Plaut et al, 2003). The role of TGF-β1 has been studied primarily during mammary development and lactation in rodents, with varying results depending on timing and c s o ra s or i ro ac or-o a ary remodeling during the dry period of dairy cows L. D. De Vries ,* T. Casey , † 1 H. Dover ,* M. J. VandeHaar ,* and K. Plaut † location of expression.…”

Section: Introductionmentioning

confidence: 99%

Effects of transforming growth factor-β on mammary remodeling during the dry period of dairy cows

Vries

Casey

Dover

et al. 2011

Journal of Dairy Science

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Mammary remodeling in dairy cows involves coordinated changes in stromal and epithelial tissue. Tissue remodeling is characterized by changes in cell proliferation, activation of fibroblasts into myofibroblasts, and changes in extracellular matrix content. Transforming growth factor β-1 (TGF-β1) increases differentiation of fibroblasts to myofibroblasts, regulates expression of extracellular matrix proteins and proteases, and has cell-type dependent effects on proliferation. The objective of this study was to determine whether TGF-β1 treatment of mammary tissue from cows in late lactation and the dry period affects cell proliferation, expression of matrix metalloproteinase-3 (MMP-3) and fibronectin (FN), and the differentiation of fibroblasts into myofibroblasts that express smooth muscle α actin (SMA). Tissue was biopsied from 7 Holstein cows at 4 time points: late lactation, 1 wk after dry-off, 3 wk before expected calving, and 1 wk before expected calving. Explants of biopsied tissue were incubated for 2h in Waymouth's medium containing insulin, hydrocortisone, and 0 or 5 ng of TGF-β1/mL; a subset of cultures was also incubated with bromodeoxyuridine to measure epithelial and stromal cell proliferation. Tissues were fixed, embedded in paraffin, sectioned, and stained by immunohistochemistry. Stage at biopsy had an overall effect on rate of epithelial and stromal cell proliferation, and TGF-β1 treatment increased rate of bromodeoxyuridine incorporation more than 2-fold in both cell types at 1 wk after dry-off. The number of fibroblasts expressing SMA was 19% higher in the intralobular stroma at 1 wk after dry-off compared with that at 1 wk before expected calving, and the percentage of activated fibroblasts tended to be higher in tissue incubated with TGF-β1. Biopsy stage had an overall effect on percentage area of epithelium expressing FN and MMP-3. Incubation with TGF-β1 had no effect on percentage intralobular stroma area expressing FN or MMP-3. Effects of TGF-β1 treatment were most apparent at 1 wk after dry-off, indicating that the first week of dry period may be an ideal target for testing effects in vivo.

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Effect of Transforming Growth Factor-beta (TGF-β) on Mammary Development

Cited by 12 publications

References 63 publications

Characterization of mammary stromal remodeling during the dry period

Characterization of mammary stromal remodeling during the dry period

Changes in Somatic Cell Count, Composition and Cytokine Levels in Milk from Cows with Mastitis Due to Mixed Infections

Effects of transforming growth factor-β on mammary remodeling during the dry period of dairy cows

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