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

被引：9

作者：

Zhang, Yongkang ^{[1
]}

Jiang, Yingjian ^{[1
]}

Li, Hongbo ^{[1
]}

Wang, Jiang ^{[1
]}

Li, Chang ^{[1
]}

Zhang, Dianliang ^{[1
]}

机构：

[1] Dalian Med Univ, Qingdao Municipal Hosp, Dept Gen Surg 1, 1 Jiaozhou Rd, Qingdao 266011, Shandong, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2023年 / 428卷 / 02期

基金：

中国国家自然科学基金;

关键词：

STING; Severe acute pancreatitis; Intestinal barrier injury; MORTALITY; SENSOR;

D O I：

10.1016/j.yexcr.2023.113630

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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)-beta, tumor ne-crosis factor (TNF)-alpha, 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-alpha, IL-6, INF-beta, FABP2, DAO and endotoxin levels and decreased pancreatic and intestinal histopathological injury in SAP rats; DMXAA aggravated serum AMY, LIPA, TNF-alpha, IL-6, INF-beta, 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.

引用

页数：9

共 29 条

[1] Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease [J].

Amasheh, Salah ;

Dullat, Sonja ;

Fromm, Michael ;

Schulzke, Joerg D. ;

Buhr, Heinz J. ;

Kroesen, Anton J. .

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 2009, 24 (10) :1149-1156

[2] STING is a direct innate immune sensor of cyclic di-GMP [J].

Burdette, Dara L. ;

Monroe, Kathryn M. ;

Sotelo-Troha, Katia ;

Iwig, Jeff S. ;

Eckert, Barbara ;

Hyodo, Mamoru ;

Hayakawa, Yoshihiro ;

Vance, Russell E. .

NATURE, 2011, 478 (7370) :515-U111

[3] Localized and systemic bacterial infections in necrotizing pancreatitis submitted to surgical necrosectomy or percutaneous drainage of necrotic secretions [J].

Cacopardo, Bruno ;

Pinzone, Marilia Rita ;

Berretta, Salvatore ;

Fisichella, Rossella ;

Di Vita, Maria ;

Zanghi, Guido ;

Cappellani, Alessandro ;

Nunnari, Giuseppe ;

Zanghi, Antonio .

BMC SURGERY, 2013, 13

[4] The role of intestinal mucosa injury induced by intra-abdominal hypertension in the development of abdominal compartment syndrome and multiple organ dysfunction syndrome [J].

Cheng, Juntao ;

Wei, Zhiyi ;

Liu, Xia ;

Li, Ximei ;

Yuan, Zhiqiang ;

Zheng, Jiang ;

Chen, Xiaodong ;

Xiao, Guangxia ;

Li, Xiaoyi .

CRITICAL CARE, 2013, 17 (06)

[5]

CHIU CJ, 1970, ARCH SURG-CHICAGO, V101, P478

[6]

Dervenis Christos, 2003, J Hepatobiliary Pancreat Surg, V10, P415, DOI 10.1007/s00534-002-0727-5

[7] Targeting STING with covalent small-molecule inhibitors [J].

Haag, Simone M. ;

Gulen, Muhammet F. ;

Reymond, Luc ;

Gibelin, Antoine ;

Abrami, Laurence ;

Decout, Alexiane ;

Heymann, Michael ;

van der Goot, F. Gisou ;

Turcatti, Gerardo ;

Behrendt, Rayk ;

Ablasser, Andrea .

NATURE, 2018, 559 (7713) :269-+

[8] STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling [J].

Ishikawa, Hiroki ;

Barber, Glen N. .

NATURE, 2008, 455 (7213) :674-U74

[9] STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity [J].

Ishikawa, Hiroki ;

Ma, Zhe ;

Barber, Glen N. .

NATURE, 2009, 461 (7265) :788-U40

[10] Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects [J].

Li, Xiao-Dong ;

Wu, Jiaxi ;

Gao, Daxing ;

Wang, Hua ;

Sun, Lijun ;

Chen, Zhijian J. .

SCIENCE, 2013, 341 (6152) :1390-1394

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