2. Academic Validation
  3. Effect of STING signaling on intestinal barrier damage in severe acute pancreatitis

Effect of STING signaling on intestinal barrier damage in severe acute pancreatitis

  • Exp Cell Res. 2023 May 17;428(2):113630. doi: 10.1016/j.yexcr.2023.113630.
Yongkang Zhang 1,  Yingjian Jiang 1,  Hongbo Li 1,  Jiang Wang 1,  Chang Li 1,  Dianliang Zhang 2
Affiliations

Affiliations

  • 1 Department of the First General Surgery, Qingdao Municipal Hospital, Dalian Medical University, No. 1 Jiaozhou Road, Qingdao, 266011, Shandong, China.
  • 2 Department of the First General Surgery, Qingdao Municipal Hospital, Dalian Medical University, No. 1 Jiaozhou Road, Qingdao, 266011, Shandong, China. Electronic address: qdsurg@qdu.edu.cn.
PMID: 37196844 DOI: 10.1016/j.yexcr.2023.113630
Abstract

Background: Patients with severe acute pancreatitis (SAP) have a compromised intestinal barrier with decreased barrier function and increased cell death. Intestinal epithelial cells (IECs) create a physicochemical barrier that anchors bacteria in the intestine. Recent studies have shown that the stimulator of interferons genes (STING) signaling pathway plays an important function in a number of inflammatory conditions.

Methods: The rat SAP model was established by retrograde injection of freshly prepared sodium taurocholate into the biliopancreatic duct. Serum amylase (AMY), Lipase (LIPA), interleukin (IL)-6, interferon (IFN)-β, tumor necrosis factor (TNF)-α, intestinal-type fatty acid binding protein (FABP2), diamine oxidase (DAO) and endotoxin (ET) levels were measured in rats. H&E staining was used to assess histological changes in the intestine and pancreas. The expression of intestinal epithelial cell tight junction (TJ) proteins and STING signaling pathway proteins and genes were measured by RT- PCR, Western blot and immunofluorescence staining were used to analyze. The expression of STING signaling pathway proteins in pancreas were measured by Western blot were used to analyze. TUNEL was used to detect IECs death.

Results: Upregulation of STING pathway-related proteins and genes occurred after sap-induced IECs. In addition, C-176 reduced serum AMY, LIPA, TNF-α, IL-6, INF-β, FABP2, DAO and endotoxin levels and decreased pancreatic and intestinal histopathological injury in SAP rats; DMXAA aggravated serum AMY, LIPA, TNF-α, IL-6, INF-β, FABP2, DAO and endotoxin levels and increased pancreatic and intestinal histopathological injury in SAP rats.

Conlusions: The results suggest that inhibition of STING signaling can alleviate IECs after SAP, and activation of STING signaling can aggravate IECs after SAP.

Keywords

Intestinal barrier injury; STING; Severe acute pancreatitis.

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