scholarly journals Effects of Astragaloside IV Against the TGF-β1-Induced Epithelial-to-Mesenchymal Transition in Peritoneal Mesothelial Cells by Promoting Smad 7 Expression

2015 ◽  
Vol 37 (1) ◽  
pp. 43-54 ◽  
Author(s):  
Lu Zhang ◽  
Zhenghong Li ◽  
Weiming He ◽  
Lingdong Xu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Treated Group ◽  
Mesothelial Cells ◽  
Vehicle Group ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Peritoneal Mesothelial Cells ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Background/Aims: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the TGF-β1/Smad signaling pathway in peritoneal mesothelial cells with an epithelial-to-mesenchymal transition (EMT). Methods: EMT of human peritoneal mesothelial cells (HMrSV5) was induced using 2 ng/ml TGF-β1. Cells were randomly divided into a vehicle group, a vehicle group with AS-IV, a TGF-β1 treated group, and a TGF-β1 treated group receiving varied doses of AS-IV or NAC. Real-time quantitative PCR and western blot were used to detect the expression of genes and proteins associated with the TGF-β1/Smad signaling pathway and EMT. DCFH-DA was used to detect the generation of ROS in HMrSV5 cells, and a transwell migration assay was used to verify the capacity of AS-IV to inhibit EMT in HMrSV5 cells. Lentiviruses were used as carriers for the overexpression or knockdown of the Smad7 gene. Results: Expression levels of E-cadherin (epithelial marker) was decreased and vimentin, α-SMA (EMT markers) and collagen I (extracellular matrix protein) phospho-Smad2/3, Snail1 and Snail2 was increased significantly in the TGF-β1-treated HMrSV5 cells. AS-IV was associated with downregulated expression of vimentin and phospho-Smad2/3 in a dose-dependent manner, while the expression of Smad7 increased. Silenced or forced expression of Smad7 verified its role in the inhibitory effect of AS-IV on TGF-β1-induced EMT in HMrSV5 cells. Conclusion: AS-IV effectively promotes the upregulation of Smad7 in the TGF-β1/Smad signaling pathway during the EMT of HMrSV5 cells, indicating its potential therapeutic effect for the control of PF.

scholarly journals TGF-β1 Receptor Inhibitor SB525334 Attenuates the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells via the TGF-β1 Signaling Pathway

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 839
Author(s):  
Jung-Yoon Heo ◽  
Jun-Young Do ◽  
Yunmee Lho ◽  
A-Young Kim ◽  
Sang-Woon Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Mesothelial Cells ◽  
Peritoneal Fibrosis ◽  
Membrane Function ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells ◽  
Emt Markers ◽  
Tgf Β1

We investigated the effect of SB525334 (TGF-β receptor type 1 (TβRI) inhibitor) on the epithelial to mesenchymal transition (EMT) signaling pathway in human peritoneal mesothelial cells (HPMCs) and a peritoneal fibrosis mouse model. In vitro experiments were performed using HPMCs. HPMCs were treated with TGF-β1 and/or SB525334. In vivo experiments were conducted with male C57/BL6 mice. The 0.1% chlorhexidine gluconate (CG) was intraperitoneally injected with or without SB52534 administration by oral gavage. Mice were euthanized after 28 days. EMT using TGF-β1-treated HPMCs included morphological changes, cell migration and invasion, EMT markers and collagen synthesis. These pathological changes were reversed by co-treatment with SB525334. CG injection was associated with an increase in peritoneal fibrosis and thickness, which functionally resulted in an increase in the glucose absorption via peritoneum. Co-treatment with SB525334 attenuated these changes. The levels of EMT protein markers and immunohistochemical staining for fibrosis showed similar trends. Immunofluorescence staining for EMT markers showed induction of transformed cells with both epithelial and mesenchymal cell markers, which decreased upon co-treatment with SB525334. SB525334 effectively attenuated the TGF-β1-induced EMT in HPMCs. Cotreatment with SB525334 improved peritoneal thickness and fibrosis and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.

scholarly journals The EIF4A3/CASC2/RORA Feedback Loop Regulates the Aggressive Phenotype in Glioblastomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Junshuang Zhao ◽  
Yang Jiang ◽  
Lian Chen ◽  
Yue Ma ◽  
Haiying Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Feedback Loop ◽  
Biological Effects ◽  
Gene Set Enrichment Analysis ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Glioblastoma (GBM) is a common and refractory subtype of high-grade glioma with a poor prognosis. The epithelial-mesenchymal transition (EMT) is an important cause of enhanced glioblastoma invasiveness and tumor recurrence. Our previous study found that retinoic acid receptor-related orphan receptor A (RORA) is a nuclear receptor and plays an important role in inhibiting proliferation and tumorigenesis of glioma. We further confirmed RORA was downregulated in GBM. Thus, we determined whether RORA was involved in the migration, invasion, and EMT of GBM. Human GBM cell lines, U87 and T98G, and patient-derived glioma stem cells (GSCs), GSC2C and GSC4D, were used for in vitro and in vivo experiments. The expressions of RORA, CASC2, and EIF4A3 in GBM cells and GSCs were detected by RT-qPCR and western blotting. The biological effects of RORA, CASC2, and EIF4A3 on GBM migration, invasion, and EMT were evaluated using the migration assay, transwell assay, immunofluorescence staining, and xenograft experiments. We found that RORA inhibited the migration, invasion, and EMT of GBM. CASC2 could bind to, maintain the stability, and promote the nuclear translocation of RORA protein. EIF4A3 could downregulate CASC2 expression via inducing its cleavage, while RORA transcriptionally inhibited EIF4A3 expression, which formed a feedback loop among EIF4A3/CASC2/RORA. Moreover, gene set enrichment analysis (GSEA) and in vitro and in vivo experiments showed RORA inhibited the aggressiveness of GBM by negatively regulating the TGF-β1/Smad signaling pathway. Therefore, The EIF4A3/CASC2/RORA feedback loop regulated TGF-β1/Smad signaling pathway might become a promising therapeutic strategy for GBM treatment.

scholarly journals Bleomycin (BLM) Induces Epithelial-to-Mesenchymal Transition in Cultured A549 Cells via the TGF-β/Smad Signaling Pathway

2016 ◽  
Vol 7 (11) ◽  
pp. 1557-1564 ◽  
Author(s):  
Kui-Jun Chen ◽  
Qing Li ◽  
Cang-mei Wen ◽  
Zhao-Xia Duan ◽  
Jie yuan Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway

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.

scholarly journals TGFβ1-Smad Signaling Pathway Participates in Interleukin-33 Induced Epithelial-to-Mesenchymal Transition of A549 Cells

2018 ◽  
Vol 50 (2) ◽  
pp. 757-767 ◽  
Author(s):  
Qiu-Yue Tan ◽  
Zhen-Shun  Cheng
Keyword(s):  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Control Group ◽  
Western Blot Assay ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Interleukin 33 ◽  
Smad Signaling Pathway ◽  
Receptor Inhibitor

Backgrounds/Aims: Epithelial-to-mesenchymal transition (EMT) has been proven to be involved in development and progression of pulmonary fibrosis. This study aims to investigate the role of transforming growth factor β1 (TGFβ1)-smad signaling pathway in the interleukin-33 (IL-33) induced EMT. Methods: The human type II alveolar epithelial cell line, A549, and small airway epithelial cells (SAEC) were cultured and divided into 4 groups including Control, LY-2109761 (TGFβ receptor inhibitor), IL-33 and IL-33+LY-2109761 group. Expression of TGFβ1, E-cadherin (E-cad) and α-smooth muscle actin (α-SMA) were examined by using real-time PCR (RT-PCR) and western blot assay, respectively. The smad3 signaling pathway factors, including smad3 and phosphorylated smad3 (p-smad3), were also detected by using western blot assay. Results: IL-33 significantly activated T1/ST2 expression in A549 cells (P< 0.05). TGFβ1 receptor inhibitor significantly suppressed the IL-33 caused down-expression of E-cad compared to IL-33 alone (P< 0.05). IL-33 significantly increased the α-SMA levels compared to Control group (P< 0.05) and TGFβ1 receptor inhibitor inhibited the other effects of IL-33. IL-33 significantly enhanced the levels of TGFβ1 compared to Control group (P< 0.05). TGFβ1 receptor inhibitor suppressed the IL-33 induced up-expression of p-smad3. Conclusion: The TGFβ1-smad signaling pathway participates in the IL-33 induced epithelial-to-mesenchymal transition of A549 cells.

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