Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain-mediated C/EBPβ and NFκ B cleavage

2015 ◽  
Vol 60 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Sheng-Mao Wu ◽  
Wan-Yu Lin ◽  
Chin-Chang Shen ◽  
Hung-Chuan Pan ◽  
Wang Keh-Bin ◽  
...  
Keyword(s):  
Er Stress ◽  
Epithelial Mesenchymal Transition ◽  
Peritoneal Dissemination ◽  
Stress Signaling ◽  
Mesenchymal Transition

scholarly journals Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 348 ◽  
Author(s):  
Ravindran ◽  
Pasha ◽  
Agouni ◽  
Munusamy
Keyword(s):  
Er Stress ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Cell Injury ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Mesenchymal Transition

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN. However, their exact role in the pathophysiology of DN remains unclear. Here, we examined the effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high glucose conditions on naïve RPTCs in vitro. Our results showed significant increases in the levels of phosphorylated forms of 4E-binding protein 1 and ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2α (an ER stress marker), alpha smooth muscle actin (an EMT marker), and phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-β signaling). Together, our findings indicate that MPs activate key signaling pathways in RPTCs under high glucose conditions. Pharmacological interventions to inhibit shedding of MPs from RPTCs might serve as an effective strategy to prevent the progression of DN.

scholarly journals MicroRNAs Associated with Epithelial-Mesenchymal Transition Can Be Targeted to Inhibit Peritoneal Dissemination of Human Scirrhous Gastric Cancers

Pathobiology ◽  
2018 ◽  
Vol 85 (4) ◽  
pp. 232-246 ◽  
Author(s):  
Yoshifumi Takei ◽  
Guodong Shen ◽  
Ayami Morita-Kondo ◽  
Toshifumi Hara ◽  
Keichiro Mihara ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Peritoneal Dissemination ◽  
Mesenchymal Transition ◽  
Gastric Cancers

scholarly journals Early Elimination of Uremic Toxin Ameliorates AKI to CKD Transition

2021 ◽  
Author(s):  
Jia Huang Chen ◽  
Chia-Ter Chao ◽  
Jenq-Wen Huang ◽  
Kuan-Yu Hung ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Er Stress ◽  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Ischemia Reperfusion ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Uremic Toxin ◽  
Mesenchymal Transition ◽  
Anion Transporter

Acute kidney injury (AKI)-related fibrosis is a major driver of chronic kidney disease (CKD) development. Aberrant kidney recovery after AKI is multifactorial and still unclear. The accumulation of indoxyl sulfate (IS), a protein-bound uremic toxin, has been identified as a detrimental factor of renal fibrosis. However, the mechanisms underlying IS-related aberrant kidney recovery after AKI is still unknown. The study aims to elucidate the effects of IS in the pathogenesis of AKI to CKD transition. Our results showed that serum IS started to accumulate associated with the downregulation of tubular organic anion transporter, but not observed in the small-molecule uremic toxins of the unilateral ischemia-reperfusion injury without a contralateral nephrectomy model(UIRI). Serum IS is positively correlated with renal fibrosis and ER stress-related protein expression induction in the UIRI with a contralateral nephrectomy model (UIRI+Nx). To evaluate the effects of IS in the AKI to CKD transition, we administered indole, a precursor of IS, at the early stage of UIRI. Our results demonstrated IS potentiates renal fibrosis, senescence-associated secretory phenotype (SASP), and activation of ER, which is attenuated by synergistic AST-120 administration. Furthermore, we clearly demonstrated that IS exposure potentiated hypoxia-reperfusion (H/R) induced G2/M cell cycle arrest, epithelial-mesenchymal transition, and aggravated ER stress induction in vitro. Finally, the ER chemical chaperon, 4-PBA, successfully reversed the above-mentioned AKI to CKD transition. Taken together, early IS elimination in the early stage of AKI is likely to be a useful strategy in the prevention or treatment of the AKI to CKD transition.

IL-32 Induces Epithelial-mesenchymal Transition in Human Pulmonary Alveolar Epithelial Cells by Triggering Endoplasmic Reticulum Stress

2020 ◽  
Author(s):  
Gang Liu ◽  
Ling Gong ◽  
Honglan Zhu ◽  
Caihong Li ◽  
Pengmei Li ◽  
...  
Keyword(s):  
Er Stress ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Mesenchymal Cell ◽  
Alveolar Epithelial Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Regulated Expression ◽  
Lung Adenocarcinoma A549 ◽  
Stimulation Of

Abstract BackgroundEpithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF.MethodsHuman lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting.ResultsStimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA. ConclusionsThese results suggest that IL-32 induces EMT in A549 cells by triggering ER stress. These results suggest that IL-32 may be a novel marker for IPF.

scholarly journals IL-32 induces epithelial-mesenchymal transition by triggering endoplasmic reticulum stress in A549 cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ling Gong ◽  
Gang Liu ◽  
Honglan Zhu ◽  
Caihong Li ◽  
Pengmei Li ◽  
...  
Keyword(s):  
Er Stress ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Mesenchymal Cell ◽  
Mesenchymal Transition ◽  
Epithelial Cell Marker ◽  
Regulated Expression ◽  
Lung Adenocarcinoma A549 ◽  
Phenylbutyric Acid ◽  
Stimulation Of

Abstract Background Epithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF. Methods Human lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting. Results Stimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, Vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA. Conclusions These results suggest that IL-32 induces EMT in A549 cells by triggering ER stress, and IL-32 may be a novel marker for IPF.

Expanding horizons in iron chelation and the treatment of cancer: Role of iron in the regulation of ER stress and the epithelial–mesenchymal transition

2014 ◽  
Vol 1845 (2) ◽  
pp. 166-181 ◽  
Author(s):  
Darius J.R. Lane ◽  
Thomas M. Mills ◽  
Nurul H. Shafie ◽  
Angelica M. Merlot ◽  
Rayan Saleh Moussa ◽  
...  
Keyword(s):  
Er Stress ◽  
Epithelial Mesenchymal Transition ◽  
Iron Chelation ◽  
Mesenchymal Transition

scholarly journals Chemical Chaperone of Endoplasmic Reticulum Stress Inhibits Epithelial-Mesenchymal Transition Induced by TGF-β1 in Airway Epithelium via the c-Src Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Heung-Man Lee ◽  
Ju-Hyung Kang ◽  
Jae-Min Shin ◽  
Seoung-Ae Lee ◽  
Il-Ho Park
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Er Stress ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Inferior Turbinate ◽  
Organ Cultures ◽  
Mesenchymal Transition ◽  
Emt Markers ◽  
Src Pathway

Epithelial-mesenchymal transition (EMT) is a biological process that allows epithelial cells to assume a mesenchymal cell phenotype. EMT is considered as a therapeutic target for several persistent inflammatory airway diseases related to tissue remodeling. Herein, we investigated the role of endoplasmic reticulum (ER) stress and c-Src in TGF-β1-induced EMT. A549 cells, primary nasal epithelial cells (PNECs), and inferior nasal turbinate organ cultures were exposed to 4-phenylbutylic acid (4PBA) or PP2 and then stimulated with TGF-β1. We found that E-cadherin, vimentin, fibronectin, and α-SMA expression was increased in nasal polyps compared to inferior turbinates. TGF-β1 increased the expression of EMT markers such as E-cadherin, fibronectin, vimentin, and α-SMA and ER stress markers (XBP-1s and GRP78), an effect that was blocked by PBA or PP2 treatment. 4-PBA and PP2 also blocked the effect of TGF-β1 on migration of A549 cells and suppressed TGF-β1-induced expression of EMT markers in PNECs and organ cultures of inferior turbinate. In conclusion, we demonstrated that 4PBA inhibits TGF-β1-induced EMT via the c-Src pathway in A549 cells, PNECs, and inferior turbinate organ cultures. These results suggest an important role for ER stress and a diverse role for TGF-β1 in upper airway chronic inflammatory disease such as CRS.

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