Protocadherin 20 maintains intestinal barrier function to protect against Crohn’s disease by targeting ATF6
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE230113 | GEO | 2023/06/14
REPOSITORIES: GEO
Similar Datasets
Project description:Protocadherin 20 maintains intestinal barrier function to protect against Crohn’s disease by targeting ATF6
| PRJNA957617 | ENA
Project description:BackgroundIntestinal barrier dysfunction plays a central role in the pathological onset of Crohn's disease. We identify the cadherin superfamily member protocadherin 20 (PCDH20) as a crucial factor in Crohn's disease. Here we describe the function of PCDH20 and its mechanisms in gut homeostasis, barrier integrity, and Crohn's disease development.ResultsPCDH20 mRNA and protein expression is significantly downregulated in the colonic epithelium of Crohn's disease patients and mice with induced colitis compared with controls. In mice, intestinal-specific Pcdh20 knockout causes defects in enterocyte proliferation and differentiation, while causing morphological abnormalities. Specifically, the deletion disrupts barrier integrity by unzipping adherens junctions via β-catenin regulation and p120-catenin phosphorylation, thus aggravating colitis in DSS- and TNBS-induced colitis mouse models. Furthermore, we identify activating transcription factor 6 (ATF6), a key chaperone of endoplasmic reticulum stress, as a functional downstream effector of PCDH20. By administering a selective ATF6 activator, the impairment of intestinal barrier integrity and dysregulation of CHOP/β-catenin/p-p120-catenin pathway was reversed in Pcdh20-ablated mice with colitis and PCDH20-deficient colonic cell lines.ConclusionsPCDH20 is an essential factor in maintaining intestinal epithelial homeostasis and barrier integrity. Specifically, PCDH20 helps to protect against colitis by tightening adherens junctions through the ATF6/CHOP/β-catenin/p-p120-catenin axis.
| S-EPMC10320870 | biostudies-literature
Project description:Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms' tumour The data consists of five microarrays hybridized with methylated DNA immunoprecipitated from Wilms' tumours and from a normal foetal kidney control
2010-05-22 | E-GEOD-15027 | biostudies-arrayexpress
Project description:Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms' tumour
2009-02-27 | GSE15027 | GEO
Project description:Taste information is detected by taste cells and then transmitted to the brain through the taste nerve fibers. According to our previous data, there may be specific coding of taste quality between taste cells and nerve fibers. However, the molecular mechanisms underlying this coding specificity remain unclear. The purpose of this study was to identify candidate molecules that may regulate the specific coding. GeneChip analysis of mRNA isolated from the mice taste papillae and taste ganglia revealed that 14 members of the cadherin superfamily, which are important regulators of synapse formation and plasticity, were expressed in both tissues. Among them, protocadherin-20 (Pcdh20) was highly expressed in a subset of taste bud cells, and co-expressed with taste receptor type 1 member 3 (T1R3, a marker of sweet- or umami-sensitive taste cells) but not gustducin or carbonic anhydrase-4 (markers of bitter/sweet- and sour-sensitive taste cells, respectively) in circumvallate papillae. Furthermore, Pcdh20 expression in taste cells occurred later than T1R3 expression during the morphogenesis of taste papillae. Thus, Pcdh20 may be involved in taste quality-specific connections between differentiated taste cells and their partner neurons, thereby acting as a molecular tag for the coding of sweet and/or umami taste.
| S-EPMC7005180 | biostudies-literature
Project description:Protocadherin 12 (Pcdh12) is a transmembrane adhesive protein with homophilic adhesive properties and expressed in endothelial cells, the glycogen trophoblast cells of the placenta, and the mesangial cells of kidney glomeruli. Pcdh12-deficient mice are alive although they show alterations in placenta development. To reveal Pcdh12-associated pathways, 45,000 - Affymetrix probe arrays were used on Pcdh12 knockout and control placentas. Keywords: Comparative gene knockout results
2008-06-30 | GSE7676 | GEO
Project description:Protocadherin 12 (Pcdh12) is a transmembrane adhesive protein with homophilic adhesive properties and expressed in endothelial cells, the glycogen trophoblast cells of the placenta, and the mesangial cells of kidney glomeruli. Pcdh12-deficient mice are alive although they show alterations in placenta development. To reveal Pcdh12-associated pathways, 45,000 - Affymetrix probe arrays were used on Pcdh12 knockout and control placentas. Experiment Overall Design: To identify genes whos expression was modified by Pcdh12 deficiency, we examined global gene expression profiles of whole E12.5 knockout placentas (Pcdh12 -l-) and their wild-type (WT â Pcdh12+l+ ) littermates, using the Affymetrix Murine Genome 430 2.0 microarrays. Gestation day 12 was chosen as it is the period at which placentas already formed distinct layers, but organogenesis is still very active. Total RNA was extracted from five Pcdh12 knockout embryos and five normal placentas. RNA were tested for integrity on Agilent 2100 BioAnalyzer, prior to cRNA synthesis and chip hybridization (performed by the Institute of Genetics and Molecular and Cellular Biology, Strasbourg, France).
2008-10-18 | E-GEOD-7676 | biostudies-arrayexpress
Project description:Intestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) connects the microvilli and is required for proper organization of the brush border. The protocadherin CDHR5 is an important member of the IMAC, but it is unclear whether CDHR5 has mainly structural functions or is also involved in cellular signaling. This issue was resolved with a CDHR5 knockout mouse model. Intestinal epithelial cells were isolated from the small intestine of four wild-type and four CDHR5 knockout mice. Bulk RNA sequencing was performed to provide insight into the functions of CDHR5 in cellular signaling and gene regulation.
2023-04-13 | E-MTAB-12525 | biostudies-arrayexpress
Project description:To determine the pattern of copy number alterations that characterizes Crohn’s disease associated colorectal carcinomas (CD-CRCs), we performed array-based comparative genomic hybridization (aCGH) of CD-CRCs. As control group, we used histomorphologically similar sporadic mucinous colorectal adenocarcinomas. To gain insight into the dynamics of copy number alterations in CD associated colorectal tumor development, we additionally analyzed non-dysplastic, i.e., normal or inflamed, mucosa samples and dysplastic lesions from CD-CRC patients by aCGH. This revealed the gain of chromosome arm 5p as a distinctive feature of CD related colorectal carcinogenesis, while the overall pattern of copy number changes in CD-CRC was similar to sporadic mucinous CRC, including gains of chromosomes and chromosome arms 7, 8, 13 and 20q, and losses of 5q, 8p, 17p and 18q.
2018-06-30 | GSE113015 | GEO
Project description:Background: Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to intestinal microbiota. To assess gut bacterial community, microRNA (miRNA), and short chain fatty acid (SCFA) signatures associated with the activity of Crohn’s disease (CD). Methods: DNA, miRNA, and metabolites were extracted from stool samples of 15 CD patients, eight with active disease and seven in remission, and nine healthy individuals. Microbial, miRNA and SCFA profiles were assessed using datasets from 16s rRNA sequencing, Nanostring miRNA and GC-MS targeted analysis, respectively. Results: Pairwise comparisons showed that 11 and 27 taxa differed between controls and CD patients with active and inactive disease, respectively. Seven taxa were common to both comparisons, whereas eight taxa differed in CD patients. α-Diversity was lower in both CD groups than in controls. The levels of 13 miRNAs differed (p-value <0.05; FC >1.5) in CD patients and controls. Comparisons of controls with CD patients having active and inactive disease identified 12 and seven significantly different miRNAs, respectively. Of six SCFAs, the levels of two differed significantly (p-value <0.05, FC >1.5) in CD patients and controls, and the levels of four differed in patients with active and inactive CD. PLS-DA revealed models with high discriminatory powers (AUC >0.9) for bacteria and miRNA. The levels of 14 miRNAs and 39 bacterial taxa correlated with the level of SCFAs. Conclusion: CD-related gut dysbiosis correlates significantly with miRNA and SCFA profiling, indicating complex relationships among all these factors in response to intestinal inflammation.
2020-08-10 | GSE144535 | GEO