scholarly journals NF-κB–Dependent Snail Expression Promotes Epithelial–Mesenchymal Transition in Mastitis

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3422
Author(s):  
Haokun Liu ◽  
Ying Zhao ◽  
Yanfang Wu ◽  
Yutong Yan ◽  
Xiaoe Zhao ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mammary Epithelial Cells ◽  
Mesenchymal Cell ◽  
Vital Role ◽  
Morphological Transformation ◽  
Snail Expression ◽  
Mesenchymal Transition

Mastitis is a common and important clinical disease in ruminants. This may be associated with inflammatory fibrosis if not treated promptly. Inflammation-derived fibrosis is usually accompanied by epithelial–mesenchymal transition (EMT) in epithelial cells. However, the precise molecular mechanism underlying mastitis-induced fibrosis remains unclear. Nuclear factor kappa-B (NF-κB) and Snail are key regulators of EMT. In this study, primary goat mammary epithelial cells (GMECs) were treated with 10 μg/mL lipopolysaccharide (LPS) for 14 d to mimic the in vivo mastitis environment. After LPS treatment, the GMECs underwent mesenchymal morphological transformation and expressed mesenchymal cell markers. Snail expression was induced by LPS and was inhibited by suppression of the TLR4/NF-κB signaling pathway. Snail knockdown alleviated LPS-induced EMT and altered the expression of inflammatory cytokines. Finally, we found that the expression of key molecules of the TLR4/NF-κB/Snail signaling pathway was increased in mastitis tissues. These results suggest that Snail plays a vital role in LPS-induced EMT in GMECs and that the mechanism is dependent on the activation of the TLR4/NF-κB signaling pathway.

scholarly journals miR-21 promotes bevacizumab induced epithelial-mesenchymal transition in retinal pigment epithelial cells by regulating Snail expression via TGFβ1/smad2/3 signaling pathway

2019 ◽  
Author(s):  
Lingling Yang ◽  
Yingbin Hua ◽  
Li Zhou ◽  
Shan Song ◽  
Haifeng Xu
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Retinal Pigment Epithelial ◽  
Epithelial Mesenchymal Transition ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
Pigment Epithelial ◽  
Pigment Epithelial Cells

Abstract Background The purpose of this study was to investigate the role of microRNA-21 (miR-21) on bevacizumab (BEV)-induced Epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells in vitro. Methods Human retinal pigment epithelial cells line (ARPE-19) were exposed to clinical dosage of BEV and miR-21 expression was measured by qRT-PCR assay. The effects of miR-21 on BEV-induced EMT were examined through gain- or loss- expression of miR-21 using miR-21 mimic or inhibitor. The expression of α-smooth muscle actin (α-SMA), E-cadherin, Snail, TGFβ1 and smad2/3 were detected by western blot. TGFβ1/smad2/3 signaling was inhibited by using SB431542 and SIS3. Results Clinical dosage of BEV caused EMT and enhanced miR-21 expression in ARPE-19 cells. The inhibition of miR-21 attenuated the EMT effect of BEV, while over-expression of miR-21 promoted this activity. Snail was up-regulated by BEV and the promotion was partially suppressed by miR-21 inhibitor and aggravated by miR-21 mimic. miR-21 regulated BEV-induced TGFβ1 increasing and smad2/3 phosphorylation. The EMT and Snail expression promoted by BEV and miR-21 mimic in ARPE-19 cells was impaired by inhibition of TGFβ1/smad2/3 signaling. Conclusions miR-21 promoted BEV-induced EMT in ARPE cells through up-regulating of Snail expression via regulation of TGFβ1/smad2/3 signaling pathway. miR-21 might be a potential miRNA-based therapeutic target in reducing BEV-induced subretinal fibrosis.

scholarly journals Pseudomonas Aeruginosa Secreted Protein PA3611 Promotes Bronchial Epithelial Cells Epithelial-Mesenchymal Transition Through TGF-β1 Inducing p38/miRNA/NF-κB Pathway

2020 ◽  
Author(s):  
Lei Shu ◽  
Sixia Chen ◽  
Xiaolin Chen ◽  
Shaoqing Lin ◽  
Xingran Du ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cell ◽  
Vital Role ◽  
Bronchial Epithelial Cells ◽  
Dependent Manner ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition ◽  
Cell Markers ◽  
Tgf Β1

Abstract BackgroundPseudomonas aeruginosa (PA) is one of the important pathogens, which has been proven to colonize and cause infection in the respiratory tract of patients with structural lung diseases, and further lead to bronchial fibrosis. Epithelial-Mesenchymal Transition (EMT) of bronchial epithelial cells plays a vital role in the process of bronchial fibrosis. Up to the present, the research on bronchial epithelial cells EMT caused by secreted virulence factors of PA has not been reported. ResultsIn our present study, we found that PA3611 protein stimulation induced the bronchial epithelial cells EMT with up-regulation of mesenchymal cell markers and down-regulation of epithelial cell markers. Meantime, TGF-β1 secretion was markedly increased, IκBα expression was significantly decreased, and NF-κB p65 subunit phosphorylation was markedly enhanced, in addition, the levels of miR-3065-3p and miR-6802-3p expression and p38 MAPK phosphorylation were obviously increased in bronchial epithelial cells after PA3611 stimulation, furthermore, PA3611 was shown to promote EMT occur through TGF-β1 induced p38/miRNA/NF-Κb pathway. The function of PA3611 was also verified in PA-infected rats and results showed that △PA3611 could reduce lung inflammation and EMT. ConclusionsOverall, our results revealed that PA3611 promotes EMT via simulating the production of TGF-β1 induced p38/miRNA/NF-κB pathway-dependent manner, suggesting that PA3611 acts as a crucial virulence factor in bronchial epithelial cells EMT process and has potential use as a target for clinical treatment of bronchial EMT and fibrosis caused by chronic PA infection.

Interleukin-27 Inhibits Epithelial-Mesenchymal Transition in Ovalbumin-Induced Mice Bronchial Epithelial Cells

2021 ◽  
Vol 11 (6) ◽  
pp. 1129-1137
Author(s):  
Yuanyuan Liu ◽  
Chao He ◽  
Xin Li ◽  
Zewen Zhang ◽  
Ju Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Airway Remodeling ◽  
Bronchial Epithelial Cell ◽  
Phenotypic Marker ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition ◽  
Stat3 Phosphorylation

The epithelial-mesenchymal transition (EMT) of bronchial epithelial cells is a critical mechanism involved in transforming growth factor beta 1 (TGF-β1) induced asthma airway remodeling. Previous study has shown that interleukin 27 (IL-27) attenuates EMT in alveolar epithelial cells, but its effects on the BEAS-2B human bronchial epithelial cell line EMT remain unknown. Herein, we explored the effects of IL-27 on BEAS-2B EMT in vivo and in vitro. In the in vivo experiments, we found that IL-27 nose-drip therapy alleviated airway remodeling, increased the epithelial phenotypic marker epithelial-cadherin (E-cadherin), and decreased the mesenchymal phenotypic marker alpha-smooth muscle actin (α-SMA) compared with the asthmatic control group. We also found that IL-27 suppressed the signal transducer and activator of transcription (STAT3) in the lung tissue of asthmatic mice. in vitro, TGF-β1-induced EMT changes, including downregulation of E-cadherin and upregulation of α-SMA, were suppressed by IL-27 treatment. Additionally, STAT3 phosphorylation was activated by TGF-β1, whereas IL-27 inhibited the activation of TGF-β1 induced STAT3 phosphorylation. Our findings indicated that IL-27 could inhibit airway remodeling by attenuating bronchial epithelial cell EMT in vivo and in vitro. Therefore, IL-27 may be a beneficial therapeutic option targeting asthmatic airway remodeling.

scholarly journals SATB1 promotes epithelial-mesenchymal transition via Notch signaling pathway in colorectal cancer

2019 ◽  
Vol 17 ◽  
pp. 205873921985889
Author(s):  
Jun Tang ◽  
Jingfang Yang
Keyword(s):  
Colorectal Cancer ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Biomarker ◽  
Notch Signaling Pathway ◽  
Vital Role ◽  
Cell Models ◽  
Mesenchymal Transition ◽  
Promising Therapeutic Target

Epithelial-mesenchymal transition (EMT) is essential for initiation of colorectal cancer (CRC) metastasis, but the diver proteins of EMT remain unclear. Special AT-rich sequence-binding protein 1 (SATB1) was found to be overexpressed in CRC cell lines, and its expression level was positively correlated with CRC progression. Strikingly, EMT process was regulated by SATB1, as SATB1 overexpression upregulated E-cadherin and SATB1 knockdown inhibited N-cadherin cell models. Mechanistically, SATB1 promoted EMT-mediated CRC metastasis via activation of Notch signaling pathway. Taken together, SATB1 plays a vital role in CRC metastasis and may act as a novel prognostic biomarker and a promising therapeutic target for CRC.

196 EPITHELIAL–MESENCHYMAL TRANSITION IN EQUINE AMNIOTIC PROGENITOR CELLS INDUCES CHANGES OF THE CELL GLYCAN PROFILE

2014 ◽  
Vol 26 (1) ◽  
pp. 212
Author(s):  
A. Lange-Consiglio ◽  
G. Accogli ◽  
F. Cremonesi ◽  
S. Desantis
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Binding Sites ◽  
Epithelial Mesenchymal Transition ◽  
Lectin Binding ◽  
Mesenchymal Transition ◽  
Glycan Profile ◽  
Amniotic Epithelial Cells

Epithelial to mesenchymal transition (EMT) is the process by which epithelial cells dramatically alter their shape and motile behaviour as they differentiate into mesenchymal cells. The EMT and the reverse process, termed mesenchymal–epithelial transition, play central roles in embryogenesis. Gastrulation and neural crest formation are processes governed by EMT in amniotes. It is noteworthy that in placental mammals, the epithelial layer of amnion originates from the trophectoderm and it is continuous with the epiblast. On this basis, it is reasonable to speculate that some amniotic epithelial cells may escape the specification that accompanies gastrulation, and may retain some of the characteristics of epiblastic cells, such as pluripotency, behaving as stem cells that are able to preserve intrinsically the ability to transdifferentiate. Because it seems that malignant cells use the same mechanisms during the formation of tumours in vivo, the amniotic epithelial cells (AEC) could represent a good model to study in vitro this phenomenon that we observed to occur spontaneously in our culture conditions. The aim of this study was to characterise the glycoprotein pattern expressed in fresh or cryopreserved equine AEC, mesenchymal (AMC), and transdifferentiated cells by means of lectin histochemistry. AEC and AMC were cultured until passage (P) 3, while transdifferentiated cells at P1(EMT1) and P2 (EMT2). All cell lines were frozen for 1 month at –196°C in liquid nitrogen. The glycoanalysis was performed with a panel of twelve lectins to detect the glycans terminating with sialic acids (MAL II, SNA, PNA after sialidase digestion (K-s), K-s-DBA), galactose (PNA, RCA120, GSA I-B4,), N-acetylgalactosamine (DBA, HPA, SBA), N-acetylglucosamine (GSA II), fucose (UEA I, LTA), or with internal mannose (Con A). After freezing: 1) AEC exhibited decrease of binding sites for DBA, SBA, HPA, GSA II, and disappearance of GSA I-B4 and UEA I binders; 2) AMC displayed increase of SBA reactivity, decrease of K-s-PNA, HPA, GSA II staining, and absence of GSA I-B4 affinity; 3) EMT1 cells showed the appearance of K-s-DBA staining, the increase of K-s-PNA, RCA120, SBA, GSA I-B4, and UEA I reactivity, the decrease of MAL II, SNA, HPA, GSA II binders, and the disappearance of DBA and LTA binding sites; 4) EMT2 cells revealed the increase of K-s-PNA, GSA I-B4, UEA I affinity, the decrease of MAL II, SNA, RCA120, HPA, GSA II binders, and the lack of DBA, SBA, and LTA reactivity. In conclusion, this study demonstrates that the EMT induces changes in cell surface glycan profile of equine amniotic progenitor cells, and for the first time revealed that freezing modifies the lectin binding pattern of these cells. The observed glycan pattern modification may represent one aspect of the spontaneous complex process of EMT.

scholarly journals Metadherin–PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT–β-catenin signaling pathway

2019 ◽  
Vol 41 (2) ◽  
pp. 130-138 ◽  
Author(s):  
Kai Zhu ◽  
Yuanfei Peng ◽  
Jinwu Hu ◽  
Hao Zhan ◽  
Liuxiao Yang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Arginine Methyltransferase ◽  
Mesenchymal Transition ◽  
Functional Assays ◽  
In Vivo Experiments ◽  
Hcc Cells

Abstract Accumulating data suggest that metadherin (MTDH) may function as an oncogene. Our previous study showed that MTDH promotes hepatocellular carcinoma (HCC) metastasis via the epithelial-mesenchymal transition. In this study, we aim to further elucidate how MTDH promotes HCC metastasis. Using Co-immunoprecipitation (co-IP) and mass spectrometry, we found that MTDH can specifically bind to protein arginine methyltransferase 5 (PRMT5). Further functional assays revealed that PRMT5 overexpression promoted the proliferation and motility of HCC cells and that knockout of PRMT5 impeded the effect of MTDH. The immunohistochemistry assay/tissue microarray results showed that when MTDH was overexpressed in HCC cells, PRMT5 translocated from the nucleus to the cytoplasm, with the subsequent translocation of β-catenin from the cytoplasm to the nucleus and upregulation of the WNT–β-catenin signaling pathway. Further in vivo experiments suggested that PRMT5 and β-catenin played a pivotal role in MTDH-mediated HCC metastasis. We therefore concluded that the MTDH–PRMT5 complex promotes HCC metastasis by regulating the WNT–β-catenin signaling pathway.

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