scholarly journals The enpp4 ectonucleotidase regulates kidney patterning signalling networks in Xenopus embryos

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Karine Massé ◽  
Surinder Bhamra ◽  
Christian Paroissin ◽  
Lilly Maneta-Peyret ◽  
Eric Boué-Grabot ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Wnt Pathway ◽  
Catalytic Mechanism ◽  
Signalling Pathways ◽  
Purinergic Signalling ◽  
Bioactive Lipids ◽  
Major Site ◽  
Over Expression ◽  
Kidney Physiology ◽  
Rare Occasion

AbstractThe enpp ectonucleotidases regulate lipidic and purinergic signalling pathways by controlling the extracellular concentrations of purines and bioactive lipids. Although both pathways are key regulators of kidney physiology and linked to human renal pathologies, their roles during nephrogenesis remain poorly understood. We previously showed that the pronephros was a major site of enpp expression and now demonstrate an unsuspected role for the conserved vertebrate enpp4 protein during kidney formation in Xenopus. Enpp4 over-expression results in ectopic renal tissues and, on rare occasion, complete mini-duplication of the entire kidney. Enpp4 is required and sufficient for pronephric markers expression and regulates the expression of RA, Notch and Wnt pathway members. Enpp4 is a membrane protein that binds, without hydrolyzing, phosphatidylserine and its effects are mediated by the receptor s1pr5, although not via the generation of S1P. Finally, we propose a novel and non-catalytic mechanism by which lipidic signalling regulates nephrogenesis.

scholarly journals The enpp4 ectonucleotidase regulates kidney patterning signalling networks in Xenopus embryos

2021 ◽  
Author(s):  
Karine Masse ◽  
Surinder Bhamra ◽  
Christian Paroissin ◽  
Lilly Maneta-Peyret ◽  
Eric Boue-Grabot ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Wnt Pathway ◽  
Catalytic Mechanism ◽  
Signalling Pathways ◽  
Purinergic Signalling ◽  
Bioactive Lipids ◽  
Major Site ◽  
Over Expression ◽  
Kidney Physiology ◽  
Rare Occasion

The enpp ectonucleotidases regulate lipidic and purinergic signalling pathways by controlling the extracellular concentrations of purines and bioactive lipids. Although both pathways are key regulators of kidney physiology and linked to human renal pathologies, their roles during nephrogenesis remain poorly understood. We previously showed that the pronephros was a major site of enpp expression and now demonstrate an unsuspected role for the conserved vertebrate enpp4 protein during kidney formation in Xenopus. Enpp4 over-expression results in ectopic renal tissues and, on rare occasion, complete mini-duplication of the entire kidney. Enpp4 is required and sufficient for expression of the pronephric markers and regulates the expression of RA, Notch and Wnt pathway members. Enpp4 is a membrane protein that binds, without hydrolyzing, phosphatidylserine and its effects are mediated by the receptor s1pr5, although not via the generation of S1P. Finally, we propose a novel and surprising non-catalytic mechanism by which lipidic signalling regulates nephrogenesis.

scholarly journals Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice

Gut ◽  
2020 ◽  
pp. gutjnl-2019-320230
Author(s):  
Anne Abot ◽  
Eve Wemelle ◽  
Claire Laurens ◽  
Adrien Paquot ◽  
Nicolas Pomie ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Enteric Neurons ◽  
Signalling Pathways ◽  
Bioactive Lipids ◽  
Mu Opioid Receptors ◽  
Mu Opioid ◽  
Receptor Signalling ◽  
Pathological Conditions

ObjectiveThe enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes.DesignWe measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human.ResultsWe found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic.ConclusionsUsing a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.

scholarly journals Diverse mechanisms for activation of Wnt signalling in the ovarian tumour microenvironment

2011 ◽  
Vol 437 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Maria V. Barbolina ◽  
Rebecca J. Burkhalter ◽  
M. Sharon Stack
Keyword(s):  
Wnt Pathway ◽  
Normal Development ◽  
Tumour Microenvironment ◽  
Ovarian Tumour ◽  
Wnt Signalling ◽  
Signalling Pathways ◽  
Genetic Mutations ◽  
Pathway Activation ◽  
Ovarian Tumours ◽  
Ovarian Tumorigenesis

Wnt signalling pathways have been shown to play key roles in both normal development and tumorigenesis. Progression of many human cancers is associated with defined mutations in Wnt pathway components that result in dysregulated β-catenin-mediated gene transcription. Although Wnt pathway mutations are rare in epithelial ovarian cancer (with the exception of the endometrioid histotype), accumulating evidence supports a role for Wnt signalling in ovarian tumorigenesis in the absence of genetic mutations. The present review summarizes evidence in support of activated Wnt signalling in ovarian tumours and discusses alternative mechanisms for Wnt pathway activation in the ovarian tumour microenvironment.

Reliable scale-up of membrane protein over-expression by bacterial auto-induction: From microwell plates to pilot scale fermentations

2008 ◽  
Vol 25 (8) ◽  
pp. 588-598 ◽  
Author(s):  
Sarah E. Deacon ◽  
Peter C. J. Roach ◽  
Vincent L.G. Postis ◽  
Gareth S. A. Wright ◽  
Xiaobing Xia ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Scale Up ◽  
Pilot Scale ◽  
Over Expression ◽  
Reliable Scale

scholarly journals SSRP1 Promotes Lung Cancer Progression by Blocking the WNT Pathway and is Negatively Regulated by miRNA-28-5p

2021 ◽  
Author(s):  
Shengnan Jia ◽  
Qian Wang ◽  
Yan Jiao ◽  
Baofeng Guo ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Wnt Pathway ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Lung Cancer Cell ◽  
Over Expression ◽  
The Relationship

Abstract Background: Structure-specific recognition protein 1 (SSRP1) plays important roles in the development of various tumors. Numerous reports have described the effects of microRNAs (miRNAs) on lung cancer apoptosis, metastasis and proliferation. However, the relationship between SSRP1 and miRNAs in the development of lung cancer remains unclear. Therefore, the purpose of our study was to explore the functions of SSRP1 in the occurrence and development of lung cancer. Methods: First, we analyzed the expression of SSRP1 in human lung cancer tissues and normal tissues, and the relationship between SSRP1 gene expression and overall survival through the UALCAN and GEPIA browsers. Second, we conducted experiments in vivo and vitro to demonstrate the roles and mechanisms of SSRP1 in the occurrence and development of lung cancer and its relationship with miR-28-5p. Results: Our study demonstrated over-expression of SSRP1 in tissue sections from patients with lung cancer and in lung cancer cell lines, as validated by bioinformatics analysis. The over-expression of SSRP1 was found to be associated with lung cancer development and low overall survival rates. Silencing of SSRP1 by siRNA inhibited lung cancer proliferation, migration and invasion by blocking the WNT signaling pathway in vitro and vivo. We also verified SSRP1 was negatively regulated by miR-28-5p，as predicted by a variety of miRNA-related databases. Further studies showed that miR-28-5p mediated suppression of SSRP1 inhibited lung cancer cell proliferation. Conclusion: Therefore, our data suggested that SSRP1 promotes lung cancer progression by blocking the WNT pathway and is negatively regulated by miRNA-28-5p.

Targeting the lipids LPA and S1P and their signalling pathways to inhibit tumour progression

2007 ◽  
Vol 9 (28) ◽  
pp. 1-18 ◽  
Author(s):  
Mandi Murph ◽  
Gordon B. Mills
Keyword(s):  
Clinical Trials ◽  
Lysophosphatidic Acid ◽  
Tumour Progression ◽  
Signalling Pathways ◽  
Bioactive Lipids ◽  
Aberrant Expression ◽  
Future Directions ◽  
Cellular Processes ◽  
Sphingosine 1 Phosphate ◽  
The Many

AbstractThe bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), the enzymes that generate and degrade them, and the receptors that receive their signals are all potential therapeutic targets in cancer. LPA and S1P signalling pathways can modulate a range of cellular processes that contribute to tumourigenesis, such as proliferation and motility, and components of the signalling pathways often show aberrant expression and altered activity upon malignant transformation. This article reviews LPA- and S1P-mediated activities that might contribute to the aetiology of cancer, and examines the potential of the many antagonists that have been developed to inhibit LPA and S1P signalling pathways. In addition, the outcomes of various clinical trials using LPA- and S1P-associated targets in cancer and other diseases are described, and future directions are discussed.

scholarly journals Expression of (beta)-catenin in the developing chick myotome is regulated by myogenic signals

Development ◽  
2000 ◽  
Vol 127 (19) ◽  
pp. 4105-4113
Author(s):  
M. Schmidt ◽  
M. Tanaka ◽  
A. Munsterberg
Keyword(s):  
Gene Expression ◽  
Wnt Pathway ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Specific Gene ◽  
Beta Catenin ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Cell Specification ◽  
Myogenic Precursor

The developmental signals that govern cell specification and differentiation in vertebrate somites are well understood. However, little is known about the downstream signalling pathways involved. We have shown previously that a combination of Shh protein and Wnt1 or Wnt3a-expressing fibroblasts is sufficient to activate skeletal muscle-specific gene expression in somite explants. Here, we have examined the molecular mechanisms by which the Wnt-mediated signal acts on myogenic precursor cells. We show that chick frizzled 1 (Fz1), beta-catenin and Lef1 are expressed during somitogenesis. Lef1 and beta-catenin transcripts become restricted to the developing myotome. Furthermore, beta-catenin is expressed prior to the time at which MyoD transcripts can be detected. Expression of beta-catenin mRNA is regulated by positive and negative signals derived from neural tube, notochord and lateral plate mesoderm. These signals include Bmp4, Shh and Wnt1/Wnt3a itself. In somite explants, Fz1, beta-catenin and Lef1 are expressed prior to activation of myogenesis in response to Shh and Wnt signals. Thus, our data show that a combination of Shh and Wnt1 upregulates expression of Wnt pathway components in developing somites prior to myogenesis. Thus, Wnt1 could act through beta-catenin on cells in the myotome.

scholarly journals Dvl3 Promotes the Phenotypic Transformation of RA-FLS and Aggravation of CIA Through Wnt Pathway by Exosome Intervention.

2021 ◽  
Author(s):  
Weixing Tan ◽  
Ning Chen ◽  
Yang Qiu ◽  
Xiaomei Feng ◽  
Shuwen Li ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Wnt Pathway ◽  
Cartilage Destruction ◽  
Luciferase Reporter ◽  
Pathological Examination ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Promote Cell Proliferation ◽  
Over Expression ◽  
Phenotypic Transformation

Abstract ObjectiveThis study was performed to explore the expression pattern of Dvl3 in RA and investigate the function and mechanism of Dvl3 in RA by exosome intervention.Methods: The expression pattern of Dvl3 was examined by IHC, WB, and qPCR. Modified exosomes obtained from culturing supernatant of RA-FLS infected with Dvl3 over expression (OE) lentivirus by ultracentrifugation were administrated to the target RA-FLS. The ability of survival, migration, and the production of inflammatory factor influenced by exosomal Dvl3 were detected by CKK8 kits, Tunel, migration test, qPCR, and enzyme-linked immunosorbent assay (ELISA) respectively; Pathological examination, ELISA, and behave revaluation were performed after injection of exosomes into the articular cavity of CIA mice. The possible downstream pathways of Dvl3 were screened by qPCR and WB, and verified by double luciferase reporter experiment.ResultsThe expression level of Dvl3 was significantly increased in RA and CIA. Exosomes from the OE group could significantly promote cell proliferation activity, migration/invasion ability. The augment of TNF-α, IL-1β, IL-17, and IL-21 was observed in exosomal Dvl3-OE group. The deteriorated role of exosomal Dvl3 in collagen-induced arthritis model (CIA) has been fully demonstrated in terms of cartilage destruction, apoptosis, and inflammation. Over expression of Dvl3 was accompanied by the significant increase of β-catenin and RhoA activities.ConclusionThis study discovered the high expression of Dvl3 of exosomes derived from RA patients which may possessed the ability to promote phenotypic transformation of RA-FLS and aggravation of CIA through Wnt pathway.

scholarly journals Ssrp1 Promotes Lung Cancer Progression By Blocking The Wnt Pathway and Is Negatively Regulated By Mirna-28-5p

2021 ◽  
Author(s):  
Shengnan Jia ◽  
Qian Wang ◽  
Yan Jiao ◽  
Baofeng Guo ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Wnt Pathway ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Lung Cancer Cell ◽  
Over Expression ◽  
The Relationship

Abstract Background: Structure-specific recognition protein 1 (SSRP1) plays important roles in the development of various tumors. Numerous reports have described the effects of microRNAs (miRNAs) on lung cancer apoptosis, metastasis and proliferation. However, the relationship between SSRP1 and miRNAs in the development of lung cancer remains unclear. Therefore, the purpose of our study was to explore the functions of SSRP1 in the occurrence and development of lung cancer.Methods: First, we analyzed the expression of SSRP1 in human lung cancer tissues and normal tissues, and the relationship between SSRP1 gene expression and overall survival through the UALCAN and GEPIA browsers. Second, we conducted experiments in vivo and vitro to demonstrate the roles and mechanisms of SSRP1 in the occurrence and development of lung cancer and its relationship with miR-28-5p.Results: Our study demonstrated over-expression of SSRP1 in tissue sections from patients with lung cancer and in lung cancer cell lines, as validated by bioinformatics analysis. The over-expression of SSRP1 was found to be associated with lung cancer development and low overall survival rates. Silencing of SSRP1 by siRNA inhibited lung cancer proliferation, migration and invasion by blocking the WNT signaling pathway in vitro and vivo. We also verified SSRP1 was negatively regulated by miR-28-5p，as predicted by a variety of miRNA-related databases. Further studies showed that miR-28-5p mediated suppression of SSRP1 inhibited lung cancer cell proliferation.Conclusion: Therefore, our data suggested that SSRP1 promotes lung cancer progression by blocking the WNT pathway and is negatively regulated by miRNA-28-5p.

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