Dataset Information

Effect of knockdown of junctional genes JUP and PLEC on Small Airway Epithelial Cells (SAECs) in the context of epithelial desquamation in distal bronchioles of Idiopathic Pulmonary fibrosis (IPF) patients

ABSTRACT: JUP and PLEC are downregulated in the distal bronchioles of IPF patients. To understand the relevance of this in the epithelial sloughing (desquamation) phenotype observed in distal bronchioles of IPF patients, we knockeddown JUP and PLEC in small airway epithelial cells thats are isolated from distal bronchioles of human airway epithelium (Lonza). Bulk RNA sequencing of JUP vs Scrambled and PLEC vs Scrambled were performed. The transriptomic data suggests that JUP transcriptionally regulates the matrix synthesis and the transcription of other junctional genes in SAECs. However, no significant effect of PLEC knockdown on transcription of matrix genes, a significant reduction in junctional gene transcripts were observed in PLEC knockdown. These findings suggest that JUP and PLEC may play key roles in the regulation of epithelial integrity during homeostasis, and when desrupted can lead to epithelial desquamation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267943 | GEO | 2025/09/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background and Aims: Desmosomes play an underexplored role in intestinal epithelial homeostasis and have been linked to the pathogenesis of inflammatory bowel diseases. Here, we assessed a novel function of the desmosomal plaque protein plakoglobin (JUP) in initiating the innate immune response that facilitates intestinal inflammation. Methods: Surgical tissue samples of patients with Crohn’s Disease (CD) were collected and characterized for junctional protein changes. Mouse models using an intestinal epithelial-specific and inducible VilCreERT2-mediated conditional knockout of Jup under basal conditions and in acute dextran-sodium sulfate (DSS)-induced colitis were characterized using functional analyses, single cell and bulk sequencing. Intestinal organoids served to determine molecular mechanisms. Results: In patients with CD and in murine DSS colitis, loss of JUP was evident. Intestinal epithelial-specific knockout of Jup in mice resulted in augmented submucosal infiltration of macrophages and neutrophils and in an overall activation of the inflammasome. However, loss of intestinal barrier function, bacterial translocation or altered microbial composition were absent under basal conditions. In DSS-induced colitis, epithelial Jup-deficiency led to increased disease activity and strong activation of interleukin IL23/17-signalling compared to littermate controls with neutrophils representing the major source of IL23 under these conditions. Mechanistically, intestinal epithelial organoids lacking Jup demonstrated robust NLRP1 inflammasome activation due to p38MAPK hyperphosphorylation. This activation was evidenced by increased expression of NLRP1, IL1β, and IL18 in Jup-deficient intestinal epithelial cells, which was mitigated by p38MAPK inhibition. Conclusion: These findings point to a novel role for JUP in initiating intestinal inflammation. The loss of JUP in tissues from CD patients underscores its potential relevance in disease pathology.

Dataset Information

Effect of knockdown of junctional genes JUP and PLEC on Small Airway Epithelial Cells (SAECs) in the context of epithelial desquamation in distal bronchioles of Idiopathic Pulmonary fibrosis (IPF) patients

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets