MicroRNA-21 increases the expression level of occludin through regulating ROCK1 in prevention of intestinal barrier...

Area of Science:

• Molecular Biology
• Gastroenterology
• Microbiology

Background:

• Intestinal barrier dysfunction is a critical factor in various gastrointestinal diseases.
• MicroRNAs (miRNAs) play significant roles in regulating cellular processes, including barrier integrity.
• The specific role of miR-21 in intestinal barrier function requires further elucidation.

Purpose of the Study:

• To investigate the molecular mechanism of microRNA-21 (miR-21) in regulating tight junction (TJ)-proteins.
• To determine the protective effects of miR-21 on intestinal barrier function.
• To explore the potential of miR-21 as a therapeutic target for intestinal barrier dysfunction.

Main Methods:

• Analysis of TJ proteins and target gene expression in NCM460 cell lines with miR-21 inhibition and overexpression.
• Establishment and analysis of a miR-21 intestinal epithelial conditional knockout (IKO) mice model.
• Detection of miR-21 expression in clinical specimens from patients with acute stercoral obstruction.

Main Results:

• Rho-associated protein kinase 1 (ROCK1) was identified as a direct target gene of miR-21.
• A negative correlation was observed between miR-21 expression levels and TJ protein levels.
• miR-21 inhibition in IKO mice led to decreased TJ proteins and ROCK1, resulting in intestinal inflammation and barrier dysfunction.

Conclusions:

• MiR-21 acts as a protective factor against intestinal barrier dysfunction.
• miR-21 promotes TJ protein expression by targeting ROCK1, both in vitro and in vivo.
• These findings highlight miR-21's crucial role in maintaining intestinal barrier integrity.