scholarly journals Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Raffaele Strippoli ◽  
Roberto Moreno-Vicente ◽  
Cecilia Battistelli ◽  
Carla Cicchini ◽  
Valeria Noce ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Pathological Process ◽  
Main Role ◽  
Peritoneal Membrane ◽  
Mesenchymal Transition ◽  
Permeable Barrier ◽  
Dialysis Solutions ◽  
Functional Deterioration

Peritoneal dialysis is a form of renal replacement alternative to the hemodialysis. During this treatment, the peritoneal membrane acts as a permeable barrier for exchange of solutes and water. Continual exposure to dialysis solutions, as well as episodes of peritonitis and hemoperitoneum, can cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy, eventually leading to discontinuation of the peritoneal dialysis. Among the different events controlling this pathological process, epithelial to mesenchymal transition of mesothelial cells plays a main role in the induction of fibrosis and in subsequent functional deterioration of the peritoneal membrane. Here, the main extracellular inducers and cellular players are described. Moreover, signaling pathways acting during this process are elucidated, with emphasis on signals delivered by TGF-βfamily members and by Toll-like/IL-1βreceptors. The understanding of molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane.

scholarly journals Molecular regulation of Snai2 in development and disease

2019 ◽  
Vol 132 (23) ◽  
Author(s):  
Wenhui Zhou ◽  
Kayla M. Gross ◽  
Charlotte Kuperwasser
Keyword(s):  
Transcription Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Zinc Finger Protein ◽  
Main Role ◽  
Biological Processes ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Damage Repair

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.

Long-term Intervention with Heparins in a Rat Model of Peritoneal Dialysis

2009 ◽  
Vol 29 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Margot N. Schilte ◽  
Jesus Loureiro ◽  
Eelco D. Keuning ◽  
Piet M. ter Wee ◽  
Johanna W.A.M. Celie ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Epithelial To Mesenchymal Transition ◽  
Morphological Changes ◽  
Glucose Absorption ◽  
Peritoneal Membrane ◽  
Access Port ◽  
Mesenchymal Transition ◽  
Chronic Inflammatory Condition ◽  
Peritoneal Leukocytes

Background Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane, particularly new vessel formation and fibrosis. In addition to anticoagulant effects, heparin displays anti-inflammatory and angiostatic properties. Therefore, the effects of administration of heparins on function and morphology of the peritoneal membrane were studied in a rat PD model. Methods Rats received 10 mL conventional PD fluid (PDF) daily, with or without the addition of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally) via a mini access port. Untreated rats served as controls. After 5 weeks, a 90-minute functional peritoneal transport test was performed and tissues and peritoneal leukocytes were taken. Results PD treatment induced loss of ultrafiltration ( p < 0.01), a twofold increase in glucose absorption ( p < 0.03), increased urea transport ( p < 0.02), and loss of sodium sieving ( p < 0.03), which were also found in the PDF + heparin groups. Increased peritoneal cell influx and hyaluronan production ( p < 0.02) as well as an exchange of mast cells and eosinophils for neutrophils after PD treatment were observed in PD rats; addition of heparin did not affect those changes. Mesothelial regeneration, submesothelial blood vessel and matrix formation, and accumulation of tissue macrophages were seen in PD animals. Spindle-shaped vimentin-positive and cytokeratin-negative cells indicated either partial injury and denudation of mesothelial cells or epithelial-to-mesenchymal transition. Neither UFH nor LMWH affected any of these morphological changes. Conclusion Within 5 weeks, PD treatment induces a chronic inflammatory condition in the peritoneum, evidenced by high transport, leukocyte recruitment, tissue remodeling, and induction of spindle-shaped cells in the mesothelium. Addition of LMWH or UFH to the PDF did not prevent these adverse PDF-induced peritoneal changes.

scholarly journals Mesenchymal Conversion of Mesothelial Cells Is a Key Event in the Pathophysiology of the Peritoneum during Peritoneal Dialysis

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Manuel López-Cabrera
Keyword(s):  
Peritoneal Dialysis ◽  
Epithelial To Mesenchymal Transition ◽  
Degradation Products ◽  
Therapeutic Option ◽  
Functional Decline ◽  
Mesothelial Cells ◽  
Peritoneal Membrane ◽  
Pharmacological Agents ◽  
Membrane Function ◽  
Mesenchymal Transition

Peritoneal dialysis (PD) is a therapeutic option for the treatment of end-stage renal disease and is based on the use of the peritoneum as a semipermeable membrane for the exchange of toxic solutes and water. Long-term exposure of the peritoneal membrane to hyperosmotic PD fluids causes inflammation, loss of the mesothelial cells monolayer, fibrosis, vasculopathy, and angiogenesis, which may lead to peritoneal functional decline. Peritonitis may further exacerbate the injury of the peritoneal membrane. In parallel with these peritoneal alterations, mesothelial cells undergo an epithelial to mesenchymal transition (EMT), which has been associated with peritoneal deterioration. Factors contributing to the bioincompatibility of classical PD fluids include the high content of glucose/glucose degradation products (GDPs) and their acidic pH. New generation low-GDPs-neutral pH fluids have improved biocompatibility resulting in better preservation of the peritoneum. However, standard glucose-based fluids are still needed, as biocompatible solutions are expensive for many potential users. An alternative approach to preserve the peritoneal membrane, complementary to the efforts to improve fluid biocompatibility, is the use of pharmacological agents protecting the mesothelium. This paper provides a comprehensive review of recent advances that point to the EMT of mesothelial cells as a potential therapeutic target to preserve membrane function.

The Need for Using An Enzymatic Colorimetric Assay in Creatinine Determination of Peritoneal Dialysis Solutions

1990 ◽  
Vol 10 (1) ◽  
pp. 89-92 ◽  
Author(s):  
Liliane Larpent ◽  
Christian Verger
Keyword(s):  
Peritoneal Dialysis ◽  
Reliable Method ◽  
Colorimetric Assay ◽  
Colorimetric Method ◽  
Peritoneal Membrane ◽  
Creatinine Kinetics ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions ◽  
Enzymatic Test

The fate of the peritoneal membrane on continuous ambulatory peritoneal dialysis (CAPD) is usually evaluated through the modification of its permeability to various solutes as glucose, creatinine, and urea. Therefore, the accuracy of the methods used for measurements of creatinine is of great importance. A particular problem does exist for creatinine determination as it may be influenced by the presence of glucose. We studied a new enzymatic colorimetric method for creatinine determination in peritoneal dialysis solutions which contain high dextrose concentrations. Creatinine was measured in plasma, urine, and dialysate from 18 patients on CAPD and in pure dextrose solutions, with an enzymatic test (Boehringer Mannheim) and with Jaffe's reaction on two different analyzers: Astra (Beckman) and Eris (Merck). Creatinine results were similar with both assays (Jaffe's reaction and enzymatic test) when measured in blood and urine. However the Jaffe's reaction gave higher creatinine results than the enzymatic test (p < 0.001), when assays were performed in peritoneal dialysis solutions and in pure glucose solutions. In addition, it appeared that other components of dialysis solutions, mainly calcium chloride, influenced unpredictably the results of creatinine with the Jaffe's reaction. We conclude that specific enzymatic test is a more accurate and reliable method to evaluate creatinine kinetics through the peritoneal membrane when determined in CAPD solutions.

scholarly journals Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Yu Tian ◽  
Bo Tang ◽  
Chengye Wang ◽  
Yan Wang ◽  
Jiakai Mao ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Sirtuin 1 ◽  
Mesenchymal Transition ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Paired Tumour

AbstractOncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA) patients and evaluated levels of the USP22 gene and protein by qPCR and immunohistochemistry. Both the mRNA and protein were significantly upregulated, correlated with the malignant invasion and worse OS of iCCA. In cell cultures, USP22 overexpression increased CCA cell proliferation and mobility, and induced epithelial-to-mesenchymal transition (EMT). Upon an interaction, USP22 deubiquitinated and stabilized sirtuin-1 (SIRT1), in conjunction with Akt/ERK activation. In implantation xenografts, USP22 overexpression stimulated tumour growth and metastasis to the lungs of mice. Conversely, the knockdown by USP22 shRNA attenuated the tumour growth and invasiveness in vitro and in vivo. Furthermore, SIRT1 overexpression reversed the USP22 functional deficiency, while the knockdown acetylated TGF-β-activated kinase 1 (TAK1) and Akt. Our present study defines USP22 as a poor prognostic predictor in iCCA that cooperates with SIRT1 and facilitates tumour development.

scholarly journals Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 555
Author(s):  
Soyoung Hur ◽  
Eungyeong Jang ◽  
Jang-Hoon Lee
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Antitumor Effects ◽  
Mesenchymal Transition ◽  
Perennial Plant

Tumors are one of the most life-threatening diseases, and a variety of cancer treatment options have been continuously introduced in order to overcome cancer and improve conventional therapy. Orostachys japonica (O. japonica), which is a perennial plant belonging to the genus Orostachys of the Crassulaceae family, has been revealed to exhibit pharmacological properties against various tumors in numerous studies. The present review aimed to discuss the biological actions and underlying molecular mechanisms of O. japonica and its representative compounds—kaempferol and quercetin—against tumors. O. japonica reportedly has antiproliferative, anti-angiogenic, and antimetastatic activities against various types of malignant tumors through the induction of apoptosis and cell cycle arrest, a blockade of downstream vascular endothelial growth factor (VEGF)-VEGFR2 pathways, and the regulation of epithelial-to-mesenchymal transition. In addition, emerging studies have highlighted the antitumor efficacy of kaempferol and quercetin. Interestingly, it was found that alterations of the mitogen-activated protein kinase (MAPK) signaling cascades are involved in the pivotal mechanisms of the antitumor effects of O. japonica and its two compounds against cancer cell overgrowth, angiogenesis, and metastasis. In summary, O. japonica could be considered a preventive and therapeutic medicinal plant which exhibits antitumor actions by reversing altered patterns of MAPK cascades, and kaempferol and quercetin might be potential components that can contribute to the efficacy and underlying mechanism of O. japonica.

scholarly journals Molecular mechanisms underpinning sarcomas and implications for current and future therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Victoria Damerell ◽  
Michael S. Pepper ◽  
Sharon Prince
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Cells Of Origin ◽  
Novel Treatment Strategies ◽  
Future Therapy

AbstractSarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but there is now mounting evidence that they originate from mesenchymal stromal/stem cells (MSCs). To identify novel treatment strategies for sarcomas, research in recent years has adopted a mechanism-based search for molecular markers for targeted therapy which has included recapitulating sarcomagenesis using in vitro and in vivo MSC models. This review provides a comprehensive up to date overview of the molecular mechanisms that underpin sarcomagenesis, the contribution of MSCs to modelling sarcomagenesis in vivo, as well as novel topics such as the role of epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs in sarcomagenesis. It also reviews current therapeutic options including ongoing pre-clinical and clinical studies for targeted sarcoma therapy and discusses new therapeutic avenues such as targeting recently identified molecular pathways and key transcription factors.

scholarly journals Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Yi-Che Lee ◽  
Yau-Sheng Tsai ◽  
Shih-Yuan Hung ◽  
Tsun-Mei Lin ◽  
Sheng-Hsiang Lin ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Epithelial To Mesenchymal Transition ◽  
Mesothelial Cells ◽  
Mesenchymal Transition ◽  
Dwelling Time
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