Peritoneal fibrosis (PF) caused by long-term peritoneal dialysis is closely associated with the epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs). Moreover, the anti-fibrotic role of Arctigenin (Arc) has been reported in several fibrosis disorders. Therefore, the preventive effect of Arc on transforming growth factor-β1 (TGF-β1)-induced EMT and the underlying mechanisms in HPMCs was investigated in this study. Firstly, the PD model was established by TGF-β1 stimulation in cultured HPMCs in vitro, we found that TGF-β1 significantly increased the EMT markers (α-SMA, vimentin, and fibronectin) and plasminogen activator inhibitor type 1 (PAI-1) expressions, but decreased epithelial marker (E-cadherin). Co-treatment with Arc (10, 20, 40 μM) ameliorated TGF-β1-induced EMT in a dose-dependent manner, and the expression of PAI-1 was also inhibited by Arc, which was abrogated by restoration of PAI-1. Moreover, Arc enhanced the phosphorylated AMP-activated protein kinase (AMPK), but inhibited the phosphorylated IκBα level and nuclear translocation of nuclear factor κB (NF-κB) p65 in TGF-β1-induced HPMCs. ChIP and Luciferase reporter assays verified that the increased binding capacity of NF-κB to the promoter of PAI-1 induced by TGF-β1 was reversely attenuated by Arc in HPMCs. However, the effect of Arc on TGF-β1-induced NF-κB activation, PAI-1 expression and EMT in HPMCs was attenuated by AMPK agonist Compound C. In conclusion, these data demonstrated that Arc suppressed TGF-β1-induced EMT by activating the AMPK/NF-κB pathway to inhibit PAI-1 expression in HPMCs. Therefore, Arc might act as a potential therapeutic agent for PD treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2019.09.130 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
L. Leaf Extract Dose-Dependently Modulates Oxidative Stress in the Kidney and Exerts Anti-Fibrotic and Anti-Inflammatory Properties by the Molecular Mechanisms Independent of NRF-2 Signalization Mirroring the Effects of Losartan in SHR.
Int J Mol Sci
December 2024
Department for Cardiovascular Physiology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, P.O. Box 39, 11129 Belgrade, Serbia.
Previously, we confirmed systemic antihypertensive and antioxidant properties of L. leaf extract (UE) in spontaneously hypertensive rats (SHR). Here, we aimed to evaluate whether UE can alter the NO and Nrf-2 signaling to prevent local oxidative stress and kidney damage in the model of essential hypertension.
View Article and Find Full Text PDFArsenite exposure induces premature senescence and senescence-associated secretory phenotype (SASP) in human hepatocyte-derived cell line Huh-7.
Environ Health Prev Med
January 2025
Health and Environmental Risk Division, National Institute for Environmental Studies.
Background: Chronic arsenite exposure has been known to induce cancer in various organs; however, the underlying mechanisms remain elusive. The characteristic feature of carcinogenesis due to arsenic exposure is that the disease develops after a prolonged latent period, even after cessation of exposure. Our previous study revealed that arsenite exposure induces premature senescence in hepatic stellate cells and suggests that the senescence-associated secretory phenotype (SASP) factors from the senescent cells promote hepatic carcinogenesis.
View Article and Find Full Text PDFGastric cancer-derived exosomal let-7 g-5p mediated by SERPINE1 promotes macrophage M2 polarization and gastric cancer progression.
J Exp Clin Cancer Res
January 2025
Department of General Surgery, The Second Clinical Medical School, The Second Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu, 730000, China.
Background: Tumor-associated macrophages (TAMs), particularly M2-polarized TAMs, are significant contributors to tumor progression, immune evasion, and therapy resistance in gastric cancer (GC). Despite efforts to target TAM recruitment or depletion, clinical efficacy remains limited. Consequently, the identification of targets that specifically inhibit or reprogram M2-polarized TAMs presents a promising therapeutic strategy.
View Article and Find Full Text PDFSALL4 mediates SHP2 inhibition in myocardial fibroblasts through the DOT1L/H3K79me2 signaling pathway to promote the progression of myocardial infarction.
Sci Rep
December 2024
Clinical Laboratory, Hebei General Hospital, Shijiazhuang, Hebei, China.
Objective: To explore the influence of SALL4 in cardiac fibroblasts on the progression of myocardial infarction.
Methods: Analysis of genes specifically expressed in myocardial infarction by bioinformatics methods; The impact of SALL4 on myocardial infarction was assessed using mouse ultrasound experiments and Masson staining; The effect of SALL4 on the expression levels of collagen-I and collagen-III in myocardial tissue was examined by immunohistochemical staining; The migration ability of cardiac fibroblasts was evaluated using a Transwell assay; The proliferative ability of cardiac fibroblasts was tested using a CCK-8 assay; The relative fluorescence intensity of α-SMA and CTGF in cardiac fibroblasts were checked through immunofluorescence staining experiment; The expression of SALL4, DOT1L, H3K79me2, P53, SHP2, YAP, nucleus-YAP, collagen-I, α-SMA, CTGF, and PAI-1 in myocardial tissues or cardiac fibroblasts was detected using western blot analysis.
Results: SALL4-specific high expression in myocardial infarction; SALL4 intensified the alterations in the heart structure of mice with myocardial infarction and worsened the fibrosis of myocardial infarction; SALL4 also promoted the expression of SALL4, DOT1L, H3K79me2, P53, SHP2, YAP, nucleus-YAP, collagen-I, collagen-III, α-SMA, CTGF, and PAI-1 in myocardial infarction tissues and cardiac fibroblasts; Subsequently, SALL4 could enhance the immunofluorescence intensity of α-SMA and CTGF; Moreover, SALL4 could promote the proliferation and migration of cardiac fibroblasts.
G Protein-coupled Estrogen Receptor 1 (GPER1) Regulates Expression of /PAI-1 and Inhibits Tumorigenic Potential of Cervical Squamous Cell Carcinoma Cells .
Cancer Genomics Proteomics
December 2024
University Medical Center Göttingen, Department of Gynecology and Obstetrics, Göttingen, Germany
Background/aim: G protein-coupled estrogen receptor 1 (GPER1) appears to play a tumor-suppressive role in cervical squamous cell carcinoma (CSCC)GPER1 suppression leads to significantly increased expression of serpin family E member 1 (SERPINE1)/protein plasminogen activator inhibitor type 1 (PAI-1). The question arises, what role does SERPINE1/PAI-1 play in GPER1-dependent tumorigenic potential of CSCC.
Materials And Methods: SiHa and C33A CSCC cells were treated with GPER1 agonist G1 or antagonist G36.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!