scholarly journals TGF-β1 Induces EMT in Bovine Mammary Epithelial Cells Through the TGFβ1/Smad Signaling Pathway

2017 ◽  
Vol 43 (1) ◽  
pp. 82-93 ◽  
Author(s):  
Qing Chen ◽  
Wei Yang ◽  
Xixi Wang ◽  
Xueru Li ◽  
Shaopei Qi ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Mammary Epithelial Cells ◽  
Mammary Glands ◽  
Mammary Epithelial ◽  
Smad Signaling ◽  
Bovine Mammary Epithelial Cells ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Background/Aims: Transforming growth factor-β1 (TGF-β1) plays a crucial role in chronic inflammation in various tissues, and is related to inflammation-caused organ fibrogenesis associated with the epithelial-mesenchymal transition (EMT) and the deposition of the extracellular matrix (ECM). However, the effect of TGF-β1 on bovine mammary epithelial cells (BMECs) with mastitis, and its mechanism, remain unknown. Methods: We analyzed the level of TGF-β1 in inflamed mammary tissues and cells using western blotting. BMECs were treated with TGF-β1, and EMT-related gene and protein expression changes were evaluated using quantitative real-time polymerase chain reaction (qPCR), western blotting, and immunofluorescence. We also inhibited the TGF/Smad signaling pathway using a receptor inhibitor, and analyzed EMT-related protein expression by western blotting. In addition, we injected TGF-β1 into mice mammary glands to investigate whether it can cause mammary fibrosis in vivo. Results: The TGF-β1 level was up-regulated in mammary tissues with mastitis and in inducible inflammatory BMECs. TGF-β1 treatment activated the TGF/ Smad signaling pathway in BMECs during their transition to the EMT phenotype, as indicated by morphological changes from a cobblestone-like shape to a spindle-like one. TGF-β1 treatment also up-regulated the expression of α-smooth muscle actin, vimentin, and collagen I, albumin, and down-regulated the expression of E-cadherin both in mRNA level and protein level. Furthermore, TGF-β1 enhanced the gene expressions of MMP2, MMP7, and fibronectin in BMECs. TGF-β1 injection induced mice mammary infection and fibrosis. Conclusion: These findings suggested that aberrant up-regulation of TGF-β1 in bovine mastitic mammary glands might play an important role in bovine mammary fibrosis caused by unresolved inflammation.

scholarly journals Inhibition of Wilms’ Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qinlin Shi ◽  
Huan Wu ◽  
Yonglin Li ◽  
Lianju Shen ◽  
Xiaomao Tian ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Wilms Tumor ◽  
Critical Role ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Proliferation And Invasion ◽  
Tgf Β1

Wilms’ tumor (WT) is a common embryonal tumor, and nephrogenic rests play a critical role in WT development. The transforming growth factor β (TGF-β) signaling pathway is fundamental to embryo development and cell growth and proliferation. Moreover, TGF-β contributes to WT development, but the mechanisms of disease pathogenicity are unknown. This study investigated whether the TGF-β signaling pathway was involved in WT and whether blocking TβRI receptor inhibited WT growth, proliferation, and invasion. A total of 60 WT patients with clinical data and surgical specimens were evaluated. Immunohistochemistry (IHC) was used to detect the expression of TGF-β1 and P-smad2/3. In vitro, the proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) protein expression were analyzed using the CCK8 assay, wound healing assay, transwell assay, flow cytometry, and western blot, respectively. In vivo, tumor morphology, tumor size, toxicity, and EMT protein expression were analyzed in tumor-bearing mice treated with a TβRI kinase inhibitor or PBS. High protein levels of TGF-β1 and P-samd2/3 were associated with clinical stage and metastasis or invasion. TβRI inhibition effectively suppressed WT proliferation and migration and promoted apoptosis in the human WT cell line G401, consequently decreasing EMT protein expression. In addition, the TβRI kinase inhibitor significantly impaired the subcutaneous growth of WT. It is worth noting that treatment with the TβRI kinase inhibitor did not cause liver and kidney injury. Our results indicate that the TGF-β/Smad signaling pathway plays a crucial role in WT progression. Blocking the TβRI receptor may be a novel strategy to treat and prevent WT.

Kisspeptin-10 Promoting the Synthesis of Milk Fat by Inhibiting the AMPK/SIRT6 Signaling Pathway via the GPR54 in Bovine Mammary Epithelial Cells

2020 ◽  
Author(s):  
Yu Cao ◽  
Juxiong Liu ◽  
Qing Zhang ◽  
Lijun Ma ◽  
Jiaxin Wang ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Signaling Pathway ◽  
Milk Fat ◽  
Mammary Epithelial Cells ◽  
Peptide Hormone ◽  
Underlying Mechanism ◽  
Mammary Glands ◽  
Bovine Mammary Epithelial Cells ◽  
Fat Synthesis ◽  
Milk Fat Synthesis

Abstract Background Kp-10 is a peptide hormone mainly involved in the initiation tissue development in puberty. Recent studies have shown that Kp-10 is involved in fat synthesis. However, the role of Kp-10 in milk fat synthesis in lactating dairy cows has not been reported. Therefore, this study investigated the correlation between GPR54 and milk fat synthesis in dairy cows and to study the underlying mechanism in BMECs. Results The results showed that the expression of GPR54, SREBP1 and FASN in mammary glands of high-milk fat dairy cows were significantly higher than those in mammary glands of low-milk fat dairy cows. Meanwhile, 10nM Kp-10 can significantly inhibit AMPK/SIRT6 signaling pathway and promote milk fat synthesis in BMECs through its receptor GPR54. Overexpression of SIRT6 significantly reduced the acetylation level of SREBP1 and milk fat synthesis in BMECs.Conclusions These results suggested that Kp-10 inhibits the AMPK / SIRT6 signaling pathway by mediating GPR54, thereby increasing SREBP1 acetylation levels and increasing milk fat synthesis in BMECs.

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