CLOCK/BMAL1 regulation of ICC autophagy in GERD model

Exploratory Score: 0.900 Price: $0.50 gastroesophageal reflux disease primary esophageal interstitial cells of Cajal Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting CLOCK, BMAL1, PER2, CRY2 in primary esophageal interstitial cells of Cajal. Primary outcome: ICC autophagy levels and cellular ultrastructure

Description

This study investigated the roles of circadian clock genes CLOCK and BMAL1 in regulating excessive autophagy of interstitial cells of Cajal (ICCs) in gastroesophageal reflux disease (GERD). Primary esophageal ICCs were isolated and cultured, then treated with deoxycholic acid to establish an in vitro GERD autophagy model. The cells were subsequently treated with siRNA targeting CLOCK, BMAL1, or both genes in combination. The study examined cellular ultrastructure using transmission electron microscopy and measured autophagy-related proteins (LC3-II/I, Beclin-1) and circadian clock proteins (CLOCK, BMAL1, PER2, CRY2) using Western blot, immunofluorescence, and RT-PCR. The research aimed to understand how circadian rhythm regulators modulate autophagy in GERD pathogenesis and identify potential therapeutic targets.

TARGET GENE
CLOCK, BMAL1, PER2, CRY2
MODEL SYSTEM
primary esophageal interstitial cells of Cajal
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
circadian rhythm regulation, autophagy
SOURCE
extracted_from_pmid_41955950
PRIMARY OUTCOME
ICC autophagy levels and cellular ultrastructure

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.900 composite

📖 Wiki Pages

PER2 ProteinproteinCRY2 ProteinproteinCLOCK ProteinproteinBMAL1 ProteinproteinPER2 GenegeneCRY2 GenegeneLC3 (Microtubule-Associated Protein 1 Light Chain proteinLC3 ProteinproteinMAP1LC3A GenegeneCLOCK GenegeneBMAL1 (ARNTL) GenegeneLC3 (MAP1LC3) NeuronscellBeclin-1proteinautophagymechanismTH Genegene

Protocol

ICC isolation and culture, deoxycholic acid treatment (25 ΞM), siRNA transfection (CLOCK, BMAL1, or combined), transmission electron microscopy, Western blot analysis, immunofluorescence assays, RT-PCR

Expected Outcomes

Deoxycholic acid increased autophagy and circadian gene expression; CLOCK/BMAL1 silencing reduced autophagy, decreased PER2/CRY2 expression, and restored ICC ultrastructure

Success Criteria

Reduced autophagy markers (LC3-II/I, Beclin-1), improved cellular ultrastructure, decreased circadian gene expression

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