scholarly journals Galectin‐3 exacerbates ox‐LDL‐mediated endothelial injury by inducing inflammation via integrin β1‐RhoA‐JNK signaling activation

2018 ◽  
Vol 234 (7) ◽  
pp. 10990-11000 ◽  
Author(s):  
Xiumei Chen ◽  
Jianzhong Lin ◽  
Tingting Hu ◽  
Zhiyun Ren ◽  
Linnan Li ◽  
...  
Keyword(s):  
Endothelial Injury ◽  
Integrin Β1 ◽  
Jnk Signaling ◽  
Galectin 3 ◽  
Signaling Activation

Galectin-3 induces ovarian cancer cell survival and chemoresistance via TLR4 signaling activation

Tumor Biology ◽  
2016 ◽  
Vol 37 (9) ◽  
pp. 11883-11891 ◽  
Author(s):  
Guoqing Cai ◽  
Xiangdong Ma ◽  
Biliang Chen ◽  
Yanhong Huang ◽  
Shujuan Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Tlr4 Signaling ◽  
Cancer Cell Survival ◽  
Galectin 3 ◽  
Signaling Activation

scholarly journals SFRP5 mediates downregulation of the wnt5a/caveolin-1/JNK signaling pathway

2020 ◽  
Vol 247 (3) ◽  
pp. 263-272
Author(s):  
Weihua Liu ◽  
Yuqiang Ji ◽  
Haiping Chu ◽  
Mo Wang ◽  
Bin Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Endothelial Injury ◽  
Average Weight ◽  
Healthy Children ◽  
Vascular Endothelial ◽  
Obese Children ◽  
Jnk Signaling ◽  
Caveolin 1 ◽  
Jnk Signaling Pathway ◽  
Huvec Cells

This study investigated the effects of Wnt5a/caveolin/JNK signaling pathway and SFRP5 protein on ox-LDL-induced apoptosis of HUVEC cells. The difference of serological indexes between healthy average weight and obese children and the expression of Wnt 5a and SFRP5 was detected by clinical examination, and the correlation between serum SFRP5, Wnt 5a and the vascular endothelial injury was detected. HUVEC cells were induced by ox-LDL to construct an endothelial injury model, siRNA-transfected cells were used to construct downregulated SFRP5 and Wnt 5a expression groups, and recombination methods were used to construct upregulated Wnt5a and SFRP5 expression groups. The expression of Wnt 5a, caveolin-1, JNK and apoptosis-related proteins under different treatments were detected by the Western blot method, and apoptosis was detected by flow cytometry. Serological results showed that the level of Sfrp5 in obese children was significantly lower than that in healthy children, and the level of Wnt5a was significantly higher than that in healthy children. Moreover, Ln Sfrp5 was significantly negatively correlated with Ang-2 in blood circulation, ICAM-1 and E-selectin selectin, but not with VCAM-1. When Wnt5a was upregulated, the expression of caveolin-1 and JNK increased significantly, Bcl-2 decreased significantly, and the apoptotic rate increased significantly. Nevertheless, when Sfrp5 expression was upregulated, the result was the opposite. SFRP5 and Wnt5a are involved in the vascular endothelial injury. Wnt5a can promote apoptosis of HUVEC cells through Wnt5a/JNK/Caveolin-1 pathway, while SFRP5 can inhibit apoptosis by interfering with this pathway.

scholarly journals Hippo signaling promotes Ets21c-dependent apical cell extrusion in the Drosophila wing disc

2020 ◽  
Author(s):  
Xianlong Ai ◽  
Dan Wang ◽  
Junzheng Zhang ◽  
Jie Shen
Keyword(s):  
Basal Cell ◽  
Molecular Mechanisms ◽  
Apical Cell ◽  
Wing Disc ◽  
Epithelial Tissue ◽  
Hippo Signaling ◽  
Developmental Defects ◽  
Jnk Signaling ◽  
Signaling Activation ◽  
Cell Extrusion

ABSTRACTCell extrusion is a crucial regulator of epithelial tissue development and homeostasis. Epithelial cells undergoing apoptosis, bearing pathological mutations, and possessing developmental defects are actively extruded toward elimination. However, the molecular mechanisms of Drosophila epithelial cell extrusion are not fully understood. Here, we report that activation of the conserved Hippo (Hpo) signaling pathway induces both apical and basal cell extrusion in the Drosophila wing disc epithelia. We show that canonical Yorki targets Diap1, and that dMyc and Cyclin E are not required for either apical or basal cell extrusion induced by activation of this pathway. Another target gene, bantam, is only involved in basal cell extrusion, suggesting novel Hpo-regulated apical cell extrusion mechanisms. Using RNA-Seq analysis, we found that JNK signaling is activated in the extruding cells. We provide genetic evidence that JNK signaling activation is both sufficient and necessary for Hpo-regulated cell extrusion. Furthermore, we demonstrate that the ETS-domain transcription factor Ets21c, an ortholog of proto-oncogenes FLI1 and ERG, acts downstream of JNK signaling to mediate apical cell extrusion. Our findings reveal a novel molecular link between Hpo signaling and cell extrusion.SUMMARY STATEMENTActivation of Hippo signaling induces cell extrusion in the Drosophila wing epithelia, in which bantam mediates basal cell extrusion and Ets21c mediates apical cell extrusion.

scholarly journals Mucin-type O-glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis

2020 ◽  
Vol 133 (20) ◽  
pp. jcs245845 ◽  
Author(s):  
Federico Pecori ◽  
Yoshihiro Akimoto ◽  
Hisatoshi Hanamatsu ◽  
Jun-ichi Furukawa ◽  
Yasuro Shinohara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Wnt Signaling ◽  
Embryonic Stem ◽  
Cell Types ◽  
Mouse Embryonic Stem Cells ◽  
T Antigen ◽  
Intrinsic Factors ◽  
Galectin 3 ◽  
Signaling Activation

ABSTRACTMouse embryonic stem cells (ESCs) can differentiate into a range of cell types during development, and this pluripotency is regulated by various extrinsic and intrinsic factors. Mucin-type O-glycosylation has been suggested to be a potential factor in the control of ESC pluripotency, and is characterized by the addition of N-acetylgalactosamine (GalNAc) to serine or threonine residues of membrane-anchored proteins and secreted proteins. To date, the relationship between mucin-type O-glycosylation and signaling in ESCs remains undefined. Here, we identify the elongation pathway via C1GalT1 that synthesizes T antigen (Galβ1-3GalNAc) as the most prominent among mucin-type O-glycosylation modifications in ESCs. Moreover, we show that mucin-type O-glycosylation on the Wnt signaling receptor frizzled-5 (Fzd5) regulates its endocytosis via galectin-3 binding to T antigen, and that reduction of T antigen results in the exit of the ESCs from pluripotency via canonical Wnt signaling activation. Our findings reveal a novel regulatory mechanism that modulates Wnt signaling and, consequently, ESC pluripotency.This article has an associated First Person interview with the first author of the paper.

scholarly journals Different Effects of Melatonin on X-Rays-Irradiated Cancer Cells in a Dose-Dependent Manner

Dose-Response ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 155932581987727 ◽  
Author(s):  
Hao Zhu ◽  
Yong Chen ◽  
Liang-cai Bai ◽  
Xiang-rong Cao ◽  
Rui Xu
Keyword(s):  
Hela Cells ◽  
Fluorescent Microscopy ◽  
Cell Killing ◽  
Dependent Manner ◽  
X Rays ◽  
Jnk Signaling ◽  
Melatonin Administration ◽  
Dichlorofluorescein Diacetate ◽  
Signaling Activation ◽  
Dose Dependent

The purpose of this study is to investigate the effects of melatonin on the radiosensitivity of HeLa cells. Concentration from 10 to 1000 µM of melatonin was used on HeLa cells before X-rays irradiation (IR). The cellular inactivation effect was analyzed by clonogenic assay, and cell growth was measured by MTT assay at various concentrations. Ten micrometer melatonin promoted the cell-killing effects of IR, while 1000-µM melatonin prevented IR-induced cellular inactivation. Further analysis revealed that 1000-µM melatonin protected the cells from IR-induced reactive oxygen species damage, as the oxidative stress measured by fluorescent microscopy and fluorescence-activated cell sorting using 2,7-dichlorofluorescein diacetate staining. This is further confirmed by melatonin receptor agonist, which has no antioxidant capacity. A 10-µM melatonin, on the contrary, enhanced the cell-killing effects of IR by activating c-Jun NH2-terminal kinase (JNK) signaling. c-Jun NH2-terminal kinase signaling activation was indicated by Western blot of phosphorylated JNK. We used JNK inhibitor to further confirm the involvement of JNK signaling in the cell-killing enhancement of 10-µM melatonin administration. Our results suggest the importance of dose-dependent effects in melatonin application for radiotherapy.

Vitexin alleviates ox-LDL-mediated endothelial injury by inducing autophagy via AMPK signaling activation

2017 ◽  
Vol 85 ◽  
pp. 214-221 ◽  
Author(s):  
Shaoli Zhang ◽  
Changlei Guo ◽  
Zhigang Chen ◽  
Peiyong Zhang ◽  
Jianhua Li ◽  
...  
Keyword(s):  
Endothelial Injury ◽  
Ampk Signaling ◽  
Signaling Activation

TMPRSS4 upregulates uPA gene expression through JNK signaling activation to induce cancer cell invasion

2014 ◽  
Vol 26 (2) ◽  
pp. 398-408 ◽  
Author(s):  
Hye-Jin Min ◽  
Yunhee Lee ◽  
Xue-Feng Zhao ◽  
Young-Kyu Park ◽  
Myung Kyu Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Jnk Signaling ◽  
Signaling Activation

P2556TXNDC5 is a novel therapeutic target of atrial fibrosis and fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P C Wu ◽  
B C Lin ◽  
Y H Yeh ◽  
W J Chen ◽  
K C Yang
Keyword(s):  
Protein Production ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Atrial Fibrosis ◽  
Jnk Signaling ◽  
Targeted Deletion ◽  
Protein Levels ◽  
Atrial Tissue ◽  
Systemic Embolization ◽  
Signaling Activation

Abstract Background Atrial fibrillation (AF), one of the most common cardiac arrhythmias, increases the risk of stroke, systemic embolization and cardiovascular mortality. Atrial fibrosis, a hallmark of chronic AF, provides substrates to initiate/propagate fibrillation waves in the atria. There, however, lacks effective and specific therapeutics targeting atrial fibrosis. We have recently identified an endoplasmic reticulum (ER) protein thioredoxin domain containing 5 (TXNDC5) as a critical mediator of cardiac ventricular fibrosis. We hypothesized that TXNDC5 could also play an important role in the pathogenesis of atrial fibrosis and fibrillation. Purpose To determine the role of TXNDC5 in atrial fibrosis and fibrillation. Methods and results TXNDC5 transcript and protein levels were both significantly upregulated in the atrial tissue from patients with AF. In addition, TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor β1 (TGFβ1) and extracellular matrix (ECM) proteins in human atrial tissue. Knockdown of TXNDC5 in human atrial fibroblasts (hAF) attenuated TGFβ1–induced hAF activation, proliferation and ECM protein upregulation, whereas overexpression of TXNDC5 was sufficient to trigger hAF activation, proliferation and ECM protein production. Further experiments revealed that the fibrogenic effects of TXNDC5 were dependent on c-Jun N-terminal kinase (JNK) signaling. Furthermore, using α-MHC-TGFβcys33ser mice, a transgenic mouse model with cardiac-specific overexpression of constitutively active TGFβ, which develop extensive atrial fibrosis and inducible AF, we showed that TXNDC5 was strongly upregulated in the fibrotic atria of α-MHC-TGFβcys33ser mice and specifically enriched in collagen-secreting atrial fibroblasts. Targeted deletion of TXNDC5 (Txndc5−/−) in α-MHC-TGFβcys33ser mice considerably mitigated the extent of atrial fibrosis. In addition, transesophageal atrial burst pacing induced AF in 75% (3 out of 4) α-MHC-TGFβcys33ser mice, whereas knockout of Txndc5 markedly reduced the inducibility of AF (25%, 3 out of 12) in α-MHC-TGFβcys33ser mice (Figure). TXNDC5 KO Reduces AF Inducibility Conclusion The present study revealed that ER protein TXNDC5 augments atrial fibrosis by promoting cardiac fibroblast proliferation and ECM protein production via JNK signaling activation. Targeted deletion of Txndc5 protects against TGFβ induced atrial fibrosis and AF. Targeting TXNDC5, therefore, could be a promising new therapeutic approach to treat or prevent atrial fibrosis and AF.

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