VE-cadherin control of reelin secretion in vitro and in vivo

Exploratory Score: 0.850 Price: $0.50 lymphatic endothelial cells and animal models Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting CDH5 in lymphatic endothelial cells and animal models. Primary outcome: demonstration of VE-cadherin requirement for reelin secretion

Description

This experiment investigated the novel finding that VE-cadherin plays a requisite role in controlling the secretion of reelin, a lymphangiocrine glycoprotein. The researchers conducted both in vitro cell culture experiments and in vivo studies to demonstrate this regulatory relationship. Reelin is a recently appreciated factor with important roles in governing heart development and injury repair. The experiments likely involved measuring reelin secretion levels under different conditions of VE-cadherin expression or function, potentially using techniques such as ELISA, Western blotting, or immunofluorescence. The in vivo component may have involved animal models to validate the physiological relevance of this regulatory mechanism.

TARGET GENE
CDH5
MODEL SYSTEM
lymphatic endothelial cells and animal models
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
reelin secretion pathway
SOURCE
extracted_from_pmid_39232006
PRIMARY OUTCOME
demonstration of VE-cadherin requirement for reelin secretion

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%) 0.850 composite

📖 Wiki Pages

ExperimentsindexResearchersindexReelin Proteinprotein

Protocol

VE-cadherin Control of Reelin Secretion In Vitro and In Vivo Protocol

Phase 1: In Vitro siRNA Knockdown in Lymphatic Endothelial Cells (Days 1-14)

Cell Culture: Culture human lymphatic microvascular endothelial cells (HMVEC-LLy, Lonza #CC-2810) in EGM-2MV medium on gelatin-coated plates (0.1% gelatin, 1 hour, RT). Maintain at 37°C, 5% CO₂. Use cells between passages 4-7.

VE-cadherin Knockdown: Transfect subconfluent HMVEC-LLy with VE-cadherin (CDH5) siRNA (Dharmacon #J-011459-09-0005, 50 nM) or non-targeting control siRNA (D-001810-10-05) using RNAiMAX (Life Technologies). Knockdown efficiency assessed at 48h and 72h via qRT-PCR (target: ≥75% mRNA reduction) and western blot (target: ≥60% protein reduction).

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Expected Outcomes

Primary Outcomes

In Vitro VE-cadherin Requirement: VE-cadherin knockdown reduces Reelin secretion by ≥65% vs. control siRNA (p < 0.001, n≥4 biological replicates). Intracellular domain deletion (ΔICD) abolishes rescue capability (<20% restoration), confirming catenin-dependent signaling requirement.

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Success Criteria

Primary Success Criteria

Secretion Dependency: siRNA-mediated VE-cadherin knockdown must reduce Reelin secretion by ≥50% in at least 3 independent HMVEC-LLy donor preparations. Rescue with WT VE-cadherin but not ΔICD mutant must restore secretion to ≥70% of control levels.

In Vivo Confirmation: VE-cadherin deletion in adult mice must produce ≥30% reduction in lymphatic Reelin content and altered lymphatic function (either reduced contractile frequency or impaired response to shear stress) within 4 weeks of induction.

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