# SIGIRR Alleviates Intestinal Mucosal Damage in Severe Acute Pancreatitis via the TLR4 Signaling Pathway

## TL;DR

This study shows that SIGIRR helps protect the intestinal barrier in severe acute pancreatitis by reducing inflammation and regulating the TLR4 pathway.

## Contribution

The novel finding is that SIGIRR overexpression protects the intestinal barrier and modulates gut microbiota in SAP.

## Key findings

- SIGIRR overexpression reduces intestinal inflammation and improves barrier function in SAP.
- SIGIRR inhibits the TLR4 signaling pathway and reduces intestinal mucosal injury in SAP models.
- SIGIRR overexpression promotes beneficial gut microbiota and suppresses harmful pathogens.

## Abstract

Intestinal barrier dysfunction plays an important role in the development of severe acute pancreatitis (SAP). The aim of our study was to investigate the role of single immunoglobulin IL-1 receptor-related molecule (SIGIRR) and Toll-like receptor-4 (TLR4) signaling pathways in SAP intestinal barrier dysfunction.

Intestinal epithelial monolayer barrier model were established by using Caco2 and HIEC cells. The effects of lipopolysaccharide or ascites fluids from patients with SAP on intestinal epithelial barrier function were assessed. Intestinal epithelial cells and mouse models with SIGIRR overexpression and knockdown were constructed to explore the role of SIGIRR on the intestinal inflammation and the TLR4 signaling pathway.

SIGIRR expression was decreased in both intestinal epithelial cells and intestinal tissues during SAP. Overexpression of SIGIRR in intestinal epithelial cells reduced inflammation and enhanced intestinal barrier function, as evidenced by measurements such as electrical resistance and fluorescein permeability. In vivo, SIGIRR overexpression reduced intestinal mucosal injury in SAP and inhibited the TLR4 signaling pathway, whereas SIGIRR knockdown worsened these effects. Additionally, SIGIRR overexpression influenced gut microbiota composition, encouraging the growth of beneficial species and suppressing harmful pathogens.

SIGIRR plays a protective role in SAP by preserving intestinal barrier integrity and negatively regulating the TLR4 signaling pathway. Targeting SIGIRR offers a novel approach for improving SAP.