scholarly journals WNT signaling is required for peritoneal membrane angiogenesis

2018 ◽  
Vol 314 (6) ◽  
pp. F1036-F1045 ◽  
Author(s):  
Manreet Padwal ◽  
Genyang Cheng ◽  
Limin Liu ◽  
Felix Boivin ◽  
Azim S. Gangji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Wnt Signaling ◽  
Solute Transport ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Membrane Injury ◽  
Mesenchymal Transition

The wingless-type mouse mammary tumor virus integration site family (WNT) signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor-β (TGF-β)-mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis. WNT1 and WNT2 gene expression were positively correlated with peritoneal membrane solute transport in PD patients. In the mouse peritoneum, TGF-β-induced peritoneal fibrosis was associated with increased expression of WNT2 and WNT4. Peritoneal β-catenin protein was significantly upregulated after infection with adenovirus expressing TGF-β (AdTGF-β) along with elements of the WNT signaling pathway. Treatment with a β-catenin inhibitor (ICG-001) in mice with AdTGF-β-induced peritoneal fibrosis resulted in attenuation of peritoneal angiogenesis and reduced vascular endothelial growth factor. Similar results were also observed with the WNT antagonist Dickkopf-related protein (DKK)-1. In addition to this, DKK-1 blocked epithelial-mesenchymal transition and increased levels of the cell adhesion protein E-cadherin. We provide evidence that WNT signaling is active in the setting of experimental peritoneal fibrosis and WNT1 correlates with patient peritoneal membrane solute transport in PD patients. Intervention in this pathway is a possible therapy for peritoneal membrane injury.

Diallyl disulphide suppresses the cannonical Wnt signaling pathway and reverses the fibronectin-induced epithelial mesenchymal transition of A549 lung cancer cells

2019 ◽  
Vol 10 (1) ◽  
pp. 191-202 ◽  
Author(s):  
Bornita Das ◽  
Dona Sinha
Keyword(s):  
Lung Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
A549 Lung

DADS reflected the potential of reversal of FN-induced EMT by inhibition of Wnt signaling in A549 lung cancer cells.

The John F. Maher Recipient Lecture 2004: Rage in the Peritoneum

2005 ◽  
Vol 25 (1) ◽  
pp. 8-11 ◽  
Author(s):  
An S. De Vriese
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Cell Surface Receptor ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition

Several conditions in the peritoneal membrane of peritoneal dialysis (PD) patients promote the accumulation of advanced glycation end-products (AGEs), that is, the uremic state, exposure to high glucose concentrations, and exposure to glucose degradation products (GDPs). AGEs exert some of their biologic actions through binding with a cell surface receptor, termed RAGE. Interaction of AGEs with RAGE induces sustained cellular activation, including the production of the fibrogenic growth factor, transforming growth factor-beta (TGF-β). TGF-β is pivotal in the process of epithelial-to-mesenchymal transition, through which cells of epithelial origin acquire myofibroblastic characteristics. Myofibroblasts are involved in virtually all conditions of pathological fibrosis. Submesothelial fibrosis is an important feature in peritoneal biopsies of PD patients, especially of those with clinical problems. We therefore examined the role of RAGE in peritoneal fibrosis, in an animal model of uremia, of high glucose exposure, and of peritoneal dialysate exposure. All three models were characterized by accumulation of AGEs, upregulation of RAGE, and fibrosis. Antagonism of RAGE prevented the upregulation of TGF-β and fibrosis in the peritoneal membrane. We further examined the underlying mechanism of peritoneal fibrosis in the uremic model. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by co-localization of cytokeratin and α-smooth muscle actin in submesothelial and interstitial fibrotic tissue. Antagonism of RAGE prevented conversion of mesothelial cells to myofibroblasts in uremia. In conclusion, we hypothesize that accumulation of AGEs in the peritoneal membrane, as a consequence of the uremic environment, chronic exposure to high glucose, and exposure to GDPs, results in an increased expression of RAGE. The interaction of AGEs with RAGE induces peritoneal fibrosis by virtue of upregulation of TGF-β and subsequent conversion of mesothelial cells into myofibroblasts.

scholarly journals Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin

2019 ◽  
Vol 20 (21) ◽  
pp. 5391 ◽  
Author(s):  
Wörthmüller ◽  
Salicio ◽  
Oberson ◽  
Blum ◽  
Schwaller
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Expression System ◽  
Single Agent ◽  
Wnt Signaling Pathway ◽  
Tumor Formation ◽  
Mesenchymal Transition

Malignant mesothelioma (MM) is an aggressive asbestos-linked neoplasm, characterized by dysregulation of signaling pathways. Due to intrinsic or acquired chemoresistance, MM treatment options remain limited. Calretinin is a Ca2+-binding protein expressed during MM tumorigenesis that activates the FAK signaling pathway, promoting invasion and epithelial-to-mesenchymal transition. Constitutive calretinin downregulation decreases MM cells’ growth and survival, and impairs tumor formation in vivo. In order to evaluate early molecular events occurring during calretinin downregulation, we generated a tightly controlled IPTG-inducible expression system to modulate calretinin levels in vitro. Calretinin downregulation significantly reduced viability and proliferation of MM cells, attenuated FAK signaling and reduced the invasive phenotype of surviving cells. Importantly, surviving cells showed a higher resistance to cisplatin due to increased Wnt signaling. This resistance was abrogated by the Wnt signaling pathway inhibitor 3289-8625. In various MM cell lines and regardless of calretinin expression levels, blocking of FAK signaling activated the Wnt signaling pathway and vice versa. Thus, blocking both pathways had the strongest impact on MM cell proliferation and survival. Chemoresistance mechanisms in MM cells have resulted in a failure of single-agent therapies. Targeting of multiple components of key signaling pathways, including Wnt signaling, might be the future method-of-choice to treat MM.

scholarly journals Network analysis uncovers putative genes affecting resistance to tick infestation in Braford cattle skin

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Daniela D. Moré ◽  
Fernando F. Cardoso ◽  
Maurício A. Mudadu ◽  
Wilson Malagó-Jr ◽  
Claudia C. Gulias-Gomes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Tick Infestation ◽  
Wnt Signaling Pathway ◽  
Functional Enrichment ◽  
A Genome ◽  
Genetic Mechanisms ◽  
Different Levels

Abstract Background Genetic resistance in cattle is considered a suitable way to control tick burden and its consequent losses for livestock production. Exploring tick-resistant (R) and tick-susceptible (S) hosts, we investigated the genetic mechanisms underlying the variation of Braford resistance to tick infestation. Skin biopsies from four-times-artificially infested R (n = 20) and S (n = 19) hosts, obtained before the first and 24 h after the fourth tick infestation were submitted to RNA-Sequencing. Differential gene expression, functional enrichment, and network analysis were performed to identify genetic pathways and transcription factors (TFs) affecting host resistance. Results Intergroup comparisons of hosts before (Rpre vs. Spre) and after (Rpost vs. Spost) tick infestation found 51 differentially expressed genes (DEGs), of which almost all presented high variation (TopDEGs), and 38 were redundant genes. Gene expression was consistently different between R and S hosts, suggesting the existence of specific anti-tick mechanisms. In the intragroup comparisons, Rpost vs. Rpre and Spost vs. Spre, we found more than two thousand DEGs in response to tick infestation in both resistance groups. Redundant and non-redundant TopDEGs with potential anti-tick functions suggested a role in the development of different levels of resistance within the same breed. Leukocyte chemotaxis was over-represented in both hosts, whereas skin degradation and remodeling were only found in TopDEGs from R hosts. Also, these genes indicated the participation of cytokines, such as IL6 and IL22, and the activation of Wingless (WNT)-signaling pathway. A central gene of this pathway, WNT7A, was consistently modulated when hosts were compared. Moreover, the findings based on a genome-wide association study (GWAS) corroborate the prediction of the WNT-signaling pathway as a candidate mechanism of resistance. The regulation of immune response was the most relevant pathway predicted for S hosts. Members of Ap1 and NF-kB families were the most relevant TFs predicted for R and S, respectively. Conclusion This work provides indications of genetic mechanisms presented by Braford cattle with different levels of resistance in response to tick infestation, contributing to the search of candidate genes for tick resistance in bovine.

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