111 Loss of Prohibitin in Intestinal Epithelial Cells Triggers the Development of Spontaneous Ileitis in Mice Subsequent to Mitochondrial Dysfunction and Paneth Cell Defects

2015 ◽  
Vol 148 (4) ◽  
pp. S-29
Author(s):  
Jie Han ◽  
Marina Panopoulos ◽  
Bin He ◽  
Bert W. O'Malley ◽  
Sylvie Robine ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mitochondrial Dysfunction ◽  
Intestinal Epithelial Cells ◽  
Paneth Cell ◽  
Intestinal Epithelial

scholarly journals Intestinal Neurod1 expression impairs paneth cell differentiation and promotes enteroendocrine lineage specification

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hui Joyce Li ◽  
Subir K. Ray ◽  
Ning Pan ◽  
Jody Haigh ◽  
Bernd Fritzsch ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Intestinal Epithelial Cells ◽  
Paneth Cell ◽  
Substantial Reduction ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Intestinal Epithelial ◽  
Conditional Expression

AbstractTranscription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription factors and hormones. Furthermore, we observed a substantial reduction of Paneth cell marker expression, although the expressions of enterocyte-, tuft- and goblet-cell specific markers are largely not affected. Our earlier study indicated that Neurog3+ progenitor cells give rise to not only EECs but also Goblet and Paneth cells. Here we show that the conditional expression of Neurod1 restricts Neurog3+ progenitors to adopt Paneth cell fate, and promotes more pronounced EE cell differentiation, while such effects are not seen in more differentiated Neurod1+ cells. Together, our data suggest that forced expression of Neurod1 programs intestinal epithelial cells more towards an EE cell fate at the expense of the Paneth cell lineage and the effect ceases as cells mature to EE cells.

scholarly journals NF-κB2 signalling in enteroids modulates enterocyte responses to secreted factors from bone marrow-derived dendritic cells

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Lauren G. Jones ◽  
Andra Vaida ◽  
Louise M. Thompson ◽  
Felix I. Ikuomola ◽  
Jorge H. Caamaño ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Epithelial Cells ◽  
Therapeutic Potential ◽  
Intestinal Epithelial Cells ◽  
Alternative Pathway ◽  
Paneth Cell ◽  
Intestinal Epithelial ◽  
Secreted Factors

AbstractAlternative pathway NF-κB signalling regulates susceptibility towards developing inflammatory bowel disease (IBD), colitis-associated cancer and sepsis-associated intestinal epithelial cell apoptosis and shedding. However, the cell populations responsible for the perturbed alternative pathway NF-κB signalling in intestinal mucosal pathology remain unclear. In order to investigate the contribution of the epithelial compartment, we have tested whether NF-κB2 regulated transcription in intestinal epithelial cells controls the intestinal epithelial response to cytokines that are known to disrupt intestinal barrier permeability. Enteroids were generated from the proximal, middle and distal regions of small intestine (SI) from C57BL/6J wild-type mice and displayed region-specific morphology that was maintained during sub-culture. Enteroids treated with 100 ng/mL TNF were compared with corresponding regions of SI from C57BL/6J mice treated systemically with 0.33 mg/kg TNF for 1.5 h. TNF-induced apoptosis in all regions of the intestine in vitro and in vivo but resulted in Paneth cell degranulation only in proximal tissue-derived SI and enteroids. TNF also resulted in increased enteroid sphericity (quantified as circularity from two-dimensional bright field images). This response was dose and time-dependent and correlated with active caspase-3 immunopositivity. Proximal tissue-derived enteroids generated from Nfκb2−/− mice showed a significantly blunted circularity response following the addition of TNF, IFNγ, lipopolysaccharide (LPS) activated C57BL/6J-derived bone marrow-derived dendritic cells (BMDC) and secreted factors from LPS-activated BMDCs. However, Nfκb1−/− mouse-derived enteroids showed no significant changes in response to these stimuli. In conclusion, the selection of SI region is important when designing enteroid studies as region-specific identity and response to stimuli such as TNF are maintained in culture. Intestinal epithelial cells are at least partially responsible for regulating their own fate by modulating NF-κB2 signalling in response to stimuli known to be involved in multiple intestinal and systemic diseases. Future studies are warranted to investigate the therapeutic potential of intestinal epithelial NF-κB2 inhibition.

scholarly journals CFTR Deletion Confers Mitochondrial Dysfunction and Disrupts Lipid Homeostasis in Intestinal Epithelial Cells

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 836 ◽  
Author(s):  
Marie Kleme ◽  
Alain Sané ◽  
Carole Garofalo ◽  
Ernest Seidman ◽  
Emmanuelle Brochiero ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mitochondrial Dysfunction ◽  
Intestinal Epithelial Cells ◽  
Lipid Homeostasis ◽  
Intestinal Epithelial

Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells

2009 ◽  
Vol 44 (3) ◽  
pp. 173-182 ◽  
Author(s):  
Minekazu Murayama ◽  
Ryuichi Okamoto ◽  
Kiichiro Tsuchiya ◽  
Junko Akiyama ◽  
Tetsuya Nakamura ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Paneth Cell ◽  
Intestinal Epithelial ◽  
Human Intestinal Epithelial Cells

scholarly journals Histidine deficiency attenuates cell viability in rat intestinal epithelial cells by apoptosis via mitochondrial dysfunction

2017 ◽  
Vol 8 ◽  
pp. 21-28 ◽  
Author(s):  
Tatsunobu Matsui ◽  
Hiroshi Ichikawa ◽  
Tomoka Fujita ◽  
Tomohisa Takagi ◽  
Mayuko Osada-Oka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Viability ◽  
Mitochondrial Dysfunction ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

scholarly journals Tumor Necrosis Factor-α and Apoptosis Signal-Regulating Kinase 1 Control Reactive Oxygen Species Release, Mitochondrial Autophagy and C-Jun N-Terminal Kinase/P38 Phosphorylation During Necrotizing Enterocolitis

2009 ◽  
Vol 2 (5) ◽  
pp. 297-306 ◽  
Author(s):  
Naira Baregamian ◽  
Jun Song ◽  
C. Eric Bailey ◽  
John Papaconstantinou ◽  
B. Mark Evers ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mitochondrial Dysfunction ◽  
Tumor Necrosis ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial Cells ◽  
Oxygen Species ◽  
Intestinal Epithelial ◽  
Epithelial Cell Apoptosis ◽  
Necrosis Factor

Background: Oxidative stress and inflammation may contribute to the disruption of the protective gut barrier through various mechanisms; mitochondrial dysfunction resulting from inflammatory and oxidative injury may potentially be a significant source of apoptosis during necrotizing enterocolitis (NEC). Tumor necrosis factor (TNF)α is thought to generate reactive oxygen species (ROS) and activate the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway. Hence, the focus of our study was to examine the effects of TNFα/ROs on mitochondrial function, ASK1-JNK/p38 cascade activation in intestinal epithelial cells during NEC.Results: We found (a) abundant tissue TNFα and ASK1 expression throughout all layers of the intestine in neonates with NEC, suggesting that TNFα/ASK1 may be a potential source (indicators) of intestinal injury in neonates with NEC; (b) TNFα-induced rapid and transient activation of JNK/p38 apoptotic signaling in all cell lines suggests that this may be an important molecular characteristic of NEC; (c) TNFα-induced rapid and transient ROs production in RIe-1 cells indicates that mitochondria are the predominant source of ROS, demonstrated by significantly attenuated response in mitochondrial DNA-depleted (RIE-1-ρ°) intestinal epithelial cells; (d) further studies with mitochondria-targeted antioxidant PBN supported our hypothesis that effective mitochondrial ROS trapping is protective against TNFα/ROs-induced intestinal epithelial cell injury; (e) TNFα induces significant mitochondrial dysfunction in intestinal epithelial cells, resulting in increased production of mtROS, drop in mitochondrial membrane potential (MMP) and decreased oxygen consumption; (f) although the significance of mitochondrial autophagy in NEC has not been unequivocally shown, our studies provide a strong preliminary indication that TNFα/ROs-induced mitochondrial autophagy may play a role in NeC, and this process is a late phenomenon.Methods: Paraffin-embedded intestinal sections from neonates with NEC and non-inflammatory condition of the gastrointestinal tract undergoing bowel resections were analyzed for TNFα and ASK1 expression. Rat (RIE-1) and mitochondrial DNA-depleted (RIE-1-ρ°) intestinal epithelial cells were used to determine the effects of TNFα on mitochondrial function.Conclusions: Our findings suggest that TNFα induces significant mitochondrial dysfunction and activation of mitochondrial apoptotic responses, leading to intestinal epithelial cell apoptosis during NeC. Therapies directed against mitochondria/ROS may provide important therapeutic options, as well as ameliorate intestinal epithelial cell apoptosis during NeC.

scholarly journals IMP1 loss in intestinal epithelial cells promotes altered Paneth cell morphology and autophagy defects (899.2)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Emma Lundsmith ◽  
Kathryn Hamilton ◽  
Felicite Noubissi ◽  
Christopher Hahn ◽  
Vladimir Spiegelman ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Morphology ◽  
Intestinal Epithelial Cells ◽  
Paneth Cell ◽  
Intestinal Epithelial
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