ROCK1 inhibitor stabilizes E-cadherin and improves barrier function in experimental necrotizing enterocolitis

Area of Science:

• Gastroenterology
• Neonatal Medicine
• Cell Biology

Background:

• Necrotizing enterocolitis (NEC) is a severe neonatal intestinal disease linked to barrier dysfunction.
• E-cadherin maintains intestinal barrier integrity, while Rho-associated protein kinase-1 (ROCK1) regulates it.
• The role of ROCK1 in NEC-related E-cadherin disruption is not fully understood.

Purpose of the Study:

• To investigate the role of ROCK1 in E-cadherin regulation during NEC.
• To determine if ROCK1 inhibition protects against NEC-induced intestinal barrier disruption.

Main Methods:

• Utilized in vitro Caco-2 NEC models (LPS/TNFα) and a rat pup NEC model (hypoxia + bacteria-containing formula).
• Analyzed human intestinal samples from NEC patients and controls.
• Assessed E-cadherin localization, ROCK1 expression, p120-catenin association, and intestinal permeability.

Main Results:

• E-cadherin was decreased and mislocalized in NEC models and human samples.
• ROCK1 expression increased early in NEC and decreased with severity.
• ROCK1 inhibition preserved E-cadherin, improved barrier integrity, reduced apoptosis, and maintained the E-cadherin-p120 complex.

Conclusions:

• ROCK1 upregulation contributes to E-cadherin disruption and increased permeability in NEC.
• ROCK1 inhibition demonstrates protective effects by stabilizing E-cadherin and enhancing barrier function.
• This study highlights ROCK1 as a potential therapeutic target for NEC.