Differentiation of the Gastric Mucosa II. Role of gastrin in gastric epithelial cell proliferation and maturation

2006 ◽  
Vol 291 (5) ◽  
pp. G762-G765 ◽  
Author(s):  
Renu N. Jain ◽  
Linda C. Samuelson
Keyword(s):  
Genetically Engineered ◽  
Gastric Epithelial Cells ◽  
Balanced Growth ◽  
Cellular Targets ◽  
Genetically Engineered Mouse Models ◽  
Gastric Physiology ◽  
Ecl Cell ◽  
Acid Secreting ◽  
And Function

Gastrin is the principal hormonal inducer of gastric acid secretion. The cellular targets for gastrin in the stomach are the acid-secreting parietal cell and histamine-producing enterochromaffin-like (ECL) cell. Gastrin is also a growth factor, with hypergastrinemia resulting in increased proliferation of gastric progenitor cells and a thickened mucosa. This review presents insights into gastrin function revealed by genetically engineered mouse models, demonstrating a new role for gastrin in the maturation of parietal and ECL cells. Thus, gastrin regulates many aspects of gastric physiology, with tight regulation of gastrin levels required to maintain balanced growth and function of gastric epithelial cells.

Neuropathology of Mowat–Wilson Syndrome

2020 ◽  
Vol 23 (4) ◽  
pp. 322-325
Author(s):  
Miriam R. Conces ◽  
Anna Hughes ◽  
Christopher R. Pierson
Keyword(s):  
Mouse Models ◽  
Hirschsprung Disease ◽  
Genetically Engineered ◽  
Facial Dysmorphism ◽  
Genetically Engineered Mouse Models ◽  
Brain Malformations ◽  
Neuroimaging Data ◽  
The Brain ◽  
Correlate Data

Mowat–Wilson syndrome (MWS) is a syndromic form of Hirschsprung disease that is characterized by variable degrees of intellectual disability, characteristic facial dysmorphism, and a diverse set of other congenital malformations due to haploinsufficiency of ZEB2. A variety of brain malformations have been described in neuroimaging studies of MWS patients, and the role of ZEB2 in the brain has been studied in a multitude of genetically engineered mouse models that are now available. However, a paucity of autopsy information limits our ability to correlate data from neuroimaging studies and animal models with actual MWS patient tissues. Here, we report the autopsy neuropathology of a 19-year-old male patient with MWS. Autopsy neuropathology findings correlated well with the reported MWS neuroimaging data and are in keeping with data from genetically engineered MWS mouse models. This autopsy enhances our understanding of ZEB2 function in human brain development and demonstrates the reliability of MWS murine models.

Differentiation of the Gastric Mucosa I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes

2006 ◽  
Vol 291 (4) ◽  
pp. G539-G544 ◽  
Author(s):  
Duan Chen ◽  
Takeshi Aihara ◽  
Chun-Mei Zhao ◽  
Rolf Håkanson ◽  
Susumu Okabe
Keyword(s):  
Gastric Mucosa ◽  
Histidine Decarboxylase ◽  
Parietal Cells ◽  
Oxyntic Mucosa ◽  
Mucosal Integrity ◽  
Ecl Cells ◽  
Gastric Physiology ◽  
Ecl Cell ◽  
Insight Into

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK2 receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H2 receptors on the parietal cells, resulting in acid secretion. The parietal cells express H2, M3, and CCK2 receptors and somatostatin sst2 receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK2 receptor genes) and genes that are important for “cross-talk” between H2 receptors and other receptors on the parietal cell (CCK2, M3, and sst2 receptors). Such analysis may provide insight into the functional significance of gastric histamine.

scholarly journals Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3477
Author(s):  
Helge Waldum ◽  
Patricia Mjønes
Keyword(s):  
Gastric Juice ◽  
Physiological Role ◽  
Easy Access ◽  
Gastric Adenocarcinomas ◽  
Gastric Physiology ◽  
Ecl Cell ◽  
A Cell ◽  
Increased Sensitivity ◽  
Main Regulator

The stomach is an ideal organ to study because the gastric juice kills most of the swallowed microbes and, thus, creates rather similar milieu among individuals. Combined with a rather easy access to gastric juice, gastric physiology was among the first areas to be studied. During the last century, a rather complete understanding of the regulation of gastric acidity was obtained, establishing the central role of gastrin and the histamine producing enterochromaffin-like (ECL) cell. Similarly, the close connection between regulation of function and proliferation became evident, and, furthermore, that chronic overstimulation of a cell with the ability to proliferate, results in tumour formation. The ECL cell has long been acknowledged to give rise to neuroendocrine tumours (NETs), but not to play any role in carcinogenesis of gastric adenocarcinomas. However, when examining human gastric adenocarcinomas with the best methods presently available (immunohistochemistry with increased sensitivity and in-situ hybridization), it became clear that many of these cancers expressed neuroendocrine markers, suggesting that some of these tumours were of neuroendocrine, and more specifically, ECL cell origin. Thus, the ECL cell and its main regulator, gastrin, are central in human gastric carcinogenesis, which make new possibilities in prevention, prophylaxis, and treatment of this cancer.

scholarly journals TMIC-25. DISSECTING THE ROLE OF HOST GENETICS IN GLIOMA EVOLUTION USING GENETICALLY-ENGINEERED MOUSE MODELS AND THE COLLABORATIVE CROSS

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi261-vi261
Author(s):  
Kasey Skinner ◽  
Martin Ferris ◽  
Ryan Bash ◽  
Abigail Shelton ◽  
Erin Smithberger ◽  
...  
Keyword(s):  
Mouse Models ◽  
Genetically Engineered ◽  
Collaborative Cross ◽  
Host Genetics ◽  
Genetically Engineered Mouse Models

scholarly journals miR-21 Plays a Dual Role in Tumor Formation and Cytotoxic Response in Breast Tumors

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 888
Author(s):  
Tu Dan ◽  
Anuradha A. Shastri ◽  
Ajay Palagani ◽  
Simone Buraschi ◽  
Thomas Neill ◽  
...  
Keyword(s):  
Treatment Resistance ◽  
Chemotherapeutic Agents ◽  
Tumor Formation ◽  
Genetically Engineered ◽  
Poor Survival ◽  
Genetically Engineered Mouse Models ◽  
Therapeutic Modalities ◽  
Cytotoxic Therapies

Breast cancer (BrCa) relies on specific microRNAs to drive disease progression. Oncogenic miR-21 is upregulated in many cancers, including BrCa, and is associated with poor survival and treatment resistance. We sought to determine the role of miR-21 in BrCa tumor initiation, progression and treatment response. In a triple-negative BrCa model, radiation exposure increased miR-21 in both primary tumor and metastases. In vitro, miR-21 knockdown decreased survival in all BrCa subtypes in the presence of radiation. The role of miR-21 in BrCa initiation was evaluated by implanting wild-type miR-21 BrCa cells into genetically engineered mouse models where miR-21 was intact, heterozygous or globally ablated. Tumors were unable to grow in the mammary fat pads of miR-21−/− mice, and grew in ~50% of miR-21+/− and 100% in miR-21+/+ mice. The contribution of miR-21 to progression and metastases was tested by crossing miR-21−/− mice with mice that spontaneously develop BrCa. The global ablation of miR-21 significantly decreased the tumorigenesis and metastases of BrCa, while sensitizing tumors to radio- and chemotherapeutic agents via Fas/FasL-dependent apoptosis. Therefore, targeting miR-21 alone or in combination with various radio or cytotoxic therapies may represent novel and efficacious therapeutic modalities for the future treatment of BrCa patients.

scholarly journals Stat3 co-operates with mutant Ezh2Y641F to regulate gene expression and limit the anti-tumor immune response in melanoma

2021 ◽  
Author(s):  
Sarah Zimmerman ◽  
Samantha J Nixon ◽  
Leela Raj ◽  
Pei Yu Chen ◽  
Sofia Smith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Transcriptional Repression ◽  
Point Mutations ◽  
Disease Recurrence ◽  
Genetic Alterations ◽  
Genetically Engineered ◽  
Polycomb Repressive Complex 2 ◽  
Genetically Engineered Mouse Models

One of the most frequently genetically altered chromatin modifiers in melanoma is the Enhancer of Zeste Homolog 2 (EZH2), the catalytic component of the Polycomb Repressive Complex 2 (PRC2), which methylates lysine 27 on histone 3 (H3K27me3), a chromatin mark associated with transcriptional repression. Genetic alterations in EZH2 in melanoma include amplifications and activating point mutations at tyrosine 641 (Y641). The oncogenic role of EZH2 in melanoma has previously been determined; however, its downstream oncogenic mechanisms remain underexplored. Here, we found that in genetically engineered mouse models, expression of Ezh2Y641F causes up-regulation of a subset of interferon-regulated genes in melanoma cells, suggesting a potential role of the immune system in the pathogenesis of these mutations. Expression of these interferon genes was not a result of changes in H3K27me3, but through a direct and non-canonical interaction between Ezh2 and Signal Transducer And Activator of Transcription 3 (Stat3). We found that Ezh2 directly binds Stat3, and that in the presence of Ezh2Y641F mutant, Stat3 protein is hypermethylated. Expression of Stat3 was required to maintain an anti-tumor immune response and its depletion resulted in faster melanoma progression and disease recurrence. Molecularly, Stat3 and Ezh2 bind together at many genomic loci, and, in association with the rest of the PRC2 complex, repress gene expression. These results suggest that one of the oncogenic mechanisms of Ezh2-mediated melanomagenesis is through evasion of the anti-tumor immune response, and that the immunomodulatory properties of Stat3 are context dependent.

scholarly journals Oxidative Stress in Genetic Mouse Models of Parkinson’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-25 ◽  
Author(s):  
Mustafa Varçin ◽  
Eduard Bentea ◽  
Yvette Michotte ◽  
Sophie Sarre
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Models ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Gene Environment ◽  
Disease Associated Genes ◽  
Genetic Mouse Models

There is extensive evidence in Parkinson’s disease of a link between oxidative stress and some of the monogenically inherited Parkinson’s disease-associated genes. This paper focuses on the importance of this link and potential impact on neuronal function. Basic mechanisms of oxidative stress, the cellular antioxidant machinery, and the main sources of cellular oxidative stress are reviewed. Moreover, attention is given to the complex interaction between oxidative stress and other prominent pathogenic pathways in Parkinson’s disease, such as mitochondrial dysfunction and neuroinflammation. Furthermore, an overview of the existing genetic mouse models of Parkinson’s disease is given and the evidence of oxidative stress in these models highlighted. Taken into consideration the importance of ageing and environmental factors as a risk for developing Parkinson’s disease, gene-environment interactions in genetically engineered mouse models of Parkinson’s disease are also discussed, highlighting the role of oxidative damage in the interplay between genetic makeup, environmental stress, and ageing in Parkinson’s disease.

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