Atrial Natriuretic Peptide Attenuates Colitis via Inhibition of the cGAS-STING Pathway in Colonic Epithelial Cells

• Published in: International journal of biological sciences Vol. 18; no. 4; pp. 1737 - 1754
• Main Authors: Chen, Chaoyue, Zhang, Ying, Tao, Meihui, Zhao, Xi, Feng, Qinyu, Fei, Xiaoshang, Fu, Yu
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2022; Ivyspring International Publisher
• Subjects: Animals; Atrial Natriuretic Factor; Atrial natriuretic peptide; Autophagy; Bacterial infections; Biopsy; Cell culture; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colitis, Ulcerative - metabolism; Colon; Colon - metabolism; Cytokines; Dextran; Dextran Sulfate; Dextrans; Disease; Disease Models, Animal; Endoplasmic reticulum; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Homeostasis; Humans; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Interferon; Kinases; Mice; Nucleotidyltransferases - metabolism; Nucleotidyltransferases - pharmacology; Pathogenesis; Peptides; Phosphorylation; Proteins; Receptors; Remission (Medicine); Research Paper; Signal transduction; Statistical methods; Stimulators; Stress; Tumor necrosis factor-TNF; Ulcerative colitis; United States > US; China; Inflammatory bowel disease; Endoplasmic reticulum stress-induced autophagy; Atrial natriuretic peptide; STING pathway; Colonic epithelial cell; Gut barrier
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.67356

Atrial Natriuretic Peptide (ANP) has known anti-inflammatory effects. However, the role of ANP in Ulcerative colitis (UC) remains unclear. This study aimed to explore the expression and function of ANP in UC, and its potential regulatory role in the stimulator of interferon genes (STING) pathway. Human colon biopsy and serum samples were collected between September 2018 and December 2019 at Wuhan Union Hospital. Levels of ANP and its receptors and STING pathway components were detected in people with UC and mice with dextran sulfate sodium (DSS)-induced colitis. These mice and HT-29 cells were treated with ANP and an agonist of the STING pathway. The level of inflammation, STING pathway, gut barrier, and endoplasmic reticulum (ER) stress-induced autophagy were measured. We found that the levels of ANP and its receptor decreased and the STING pathway activated statistically in people with UC and the mouse model of colitis. ANP treatment attenuated DSS-induced colitis and inhibited STING pathway phosphorylation in colonic tissue and epithelial cells. An interaction between cGAS and NPR-A was verified. ANP repaired the gut barrier and inhibited ER stress-induced autophagy via the STING pathway. ANP may thus alter colonic barrier function and regulate ER stress-induced autophagy as a promising therapy for UC.