scholarly journals The basic route of nuclear‐targeted transport of IGF‐1/IGF‐1R and potential biological functions in intestinal epithelial cells

2021 ◽  
Author(s):  
Ming Xiu ◽  
Xia Huan ◽  
Yang Ou ◽  
Sha Ying ◽  
Jianmeng Wang
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Biological Functions ◽  
Targeted Transport

scholarly journals Functional screen of inflammatory bowel disease genes reveals key epithelial functions

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jessy Carol Ntunzwenimana ◽  
Gabrielle Boucher ◽  
Jean Paquette ◽  
Hugues Gosselin ◽  
Azadeh Alikashani ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Biological Functions ◽  
Functional Screen ◽  
Endogenous Expression ◽  
Causal Genes ◽  
The Impact

Abstract Background Genetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts has been more limited. Methods We identified 145 genes from IBD-associated genomic loci having endogenous expression within the intestinal epithelial cell compartment. We evaluated the impact of lentiviral transfer of the open reading frame (ORF) of these IBD genes into the HT-29 intestinal epithelial cell line via transcriptomic analyses. By comparing the genes in which expression was modulated by each ORF, as well as the functions enriched within these gene lists, we identified ORFs with shared impacts and their putative disease-relevant biological functions. Results Analysis of the transcriptomic data for cell lines expressing the ORFs for known causal genes such as HNF4a, IFIH1, and SMAD3 identified functions consistent with what is already known for these genes. These analyses also identified two major clusters of genes: Cluster 1 contained the known IBD causal genes IFIH1, SBNO2, NFKB1, and NOD2, as well as genes from other IBD loci (ZFP36L1, IRF1, GIGYF1, OTUD3, AIRE and PITX1), whereas Cluster 2 contained the known causal gene KSR1 and implicated DUSP16 from another IBD locus. Our analyses highlight how multiple IBD gene candidates can impact on epithelial structure and function, including the protection of the mucosa from intestinal microbiota, and demonstrate that DUSP16 acts a regulator of MAPK activity and contributes to mucosal defense, in part via its regulation of the polymeric immunoglobulin receptor, involved in the protection of the intestinal mucosa from enteric microbiota. Conclusions This functional screen, based on expressing IBD genes within an appropriate cellular context, in this instance intestinal epithelial cells, resulted in changes to the cell’s transcriptome that are relevant to their endogenous biological function(s). This not only helped in identifying likely causal genes within genetic loci but also provided insight into their biological functions. Furthermore, this work has highlighted the central role of intestinal epithelial cells in IBD pathophysiology, providing a scientific rationale for a drug development strategy that targets epithelial functions in addition to the current therapies targeting immune functions.

scholarly journals Functional screen of Inflammatory Bowel Disease genes reveals key epithelial functions

2021 ◽  
Author(s):  
Jessy Carol Ntunzwenimana ◽  
Gabrielle Boucher ◽  
Jean Paquette ◽  
Hugues Gosselin ◽  
Azadeh Alikashani ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Biological Functions ◽  
Functional Screen ◽  
Major Cluster ◽  
Causal Genes ◽  
The Impact

Background: Genetic studies have been tremendously successful in identifying genomic regions associated with a wide variety of phenotypes, although the success of these studies in identifying causal genes, their variants, and their functional impacts have been more limited. Methods: We identified 145 genes from IBD-associated genomic loci having endogenous expression within the intestinal epithelial cell compartment. We evaluated the impact of lentiviral transfer of the open reading frame (ORF) of these IBD genes into the HT-29 intestinal epithelial cell line via transcriptomic analyses. Comparing the genes whose expression was modulated by each ORF, as well as the functions enriched within these gene lists, identified ORFs with shared impacts and their putative disease-relevant biological functions. Results: Analysis of the transcriptomic data for cell lines expressing the ORFs for known causal genes such as HNF4a, IFIH1 and SMAD3 identified functions consistent for what is known for these genes. These analyses also identified two major cluster of genes: Cluster 1 contained the known IBD causal genes IFIH1, SBNO2, NFKB1 and NOD2, as well as genes from other IBD loci (ZFP36L1, IRF1, GIGYF1, OTUD3, AIRE and PITX1), whereas Cluster 2 contained the known causal gene KSR1 and implicated DUSP16 from another IBD locus. Our analyses highlight how multiple IBD gene candidates impact on epithelial structure and function, including the protection of the mucosa from intestinal microbiota, and demonstrate that DUSP16, acts a regulator of MAPK activity and contributes to mucosal defense, in part via its regulation of the polymeric immunoglobulin receptor, involved in the protection of the intestinal mucosa from enteric microbiota. Conclusions: This functional screen, based on expressing IBD genes within an appropriate cellular context, in this instance intestinal epithelial cells, resulted in changes to the cell's transcriptome that are relevant to their endogenous biological function(s). This not only helped in identifying likely causal genes within genetic loci but also provided insight into their biological functions. Furthermore, this work has highlighted the central role of intestinal epithelial cells in IBD pathophysiology, providing a scientific rationale for a drug development strategy that targets epithelial functions in addition to the current therapies targeting immune functions.

Three-dimensional organization and functional relationships of endocytotic compartments in pig intestinal epithelial cells

1992 ◽  
Vol 50 (1) ◽  
pp. 576-577
Author(s):  
Julian P. Heath ◽  
Buford L. Nichols ◽  
László G. Kömüves
Keyword(s):  
Electron Microscopy ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Three Dimensional ◽  
Intestinal Epithelial ◽  
Cell Surfaces ◽  
Basal Surface ◽  
Functional Relationships

The newborn pig intestine is adapted for the rapid and efficient absorption of nutrients from colostrum. In enterocytes, colostral proteins are taken up into an apical endocytotic complex of channels that transports them to target organelles or to the basal surface for release into the circulation. The apical endocytotic complex of tubules and vesicles clearly is a major intersection in the routes taken by vesicles trafficking to and from the Golgi, lysosomes, and the apical and basolateral cell surfaces.Jejunal tissues were taken from piglets suckled for up to 6 hours and prepared for electron microscopy and immunocytochemistry as previously described.

Thrombin enhances migration of intestinal epithelial cells

2001 ◽  
Vol 120 (5) ◽  
pp. A504-A504
Author(s):  
A NEUMANN ◽  
M DEPKAPRONDZINSKI ◽  
C WILHELM ◽  
K FELGENHAUER ◽  
T CASPRITZ ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial
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