Targeting palmitoyl acyltransferase ZDHHC21 improves gut epithelial barrier dysfunction resulting from burn-induced...

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Severe thermal injury in burn patients is linked to intestinal inflammation and hyperpermeability.
• This gut barrier dysfunction exacerbates systemic responses, potentially leading to sepsis and multiple organ failure.

Purpose of the Study:

• To investigate the role of zinc finger DHHC domain-containing protein-21 (ZDHHC21) in thermal injury-induced gut hyperpermeability.
• To evaluate ZDHHC21 as a potential therapeutic target for burn-induced intestinal barrier dysfunction.

Main Methods:

• Quantitative PCR to measure ZDHHC21 mRNA levels.
• Pharmacological inhibition of palmitoyl acyltransferases using 2-bromopalmitate (2-BP).
• In vitro and in vivo models of thermal injury, including ZDHHC21-deficient mice and permeability assays (ECIS, FITC-dextran).

Main Results:

• ZDHHC21 mRNA expression was upregulated by inflammatory cytokines (TNF-α-IFN-γ).
• 2-BP treatment significantly improved epithelial barrier function and reduced palmitoylation.
• Impaired ZDHHC21 function (genetic or pharmacological) attenuated thermal injury-induced gut barrier dysfunction and villus damage.

Conclusions:

• ZDHHC21 plays a critical role in mediating gut hyperpermeability following thermal injury.
• Targeting ZDHHC21 offers a promising therapeutic strategy for managing burn-induced intestinal barrier defects.