E. coli JM83 damages the mucosal barrier in Ednrb knockout mice to promote the development of Hirschsprung‑associated enterocolitis via activation of TLR4/p‑p38/NF‑κB signaling

• Published in: Molecular medicine reports Vol. 25; no. 5
• Main Authors: Zheng, Zebing, Gao, Mingjuan, Tang, Chengyan, Huang, Lu, Gong, Yuan, Liu, Yuanmei, Wang, Jian
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.05.2022; D.A. Spandidos
• Subjects: Actin; Animals; Antibodies; Colon; Disease Models, Animal; E coli; Endothelins; Enterocolitis; Enterocolitis - genetics; Enterocolitis - metabolism; Escherichia coli - metabolism; Inflammatory bowel disease; Interleukin 10; Intestinal microflora; Intestinal Mucosa - metabolism; Intestine; Laboratories; Mice; Mice, Knockout; Microbiota; Mucosa; NF-kappa B - metabolism; NF-κB protein; Pathogens; Proteins; Receptor, Endothelin B - metabolism; Receptors, Endothelin - metabolism; Signal Transduction; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor necrosis factor-α; China; endothelin receptor B; Hirschsprung‑associated enterocolitis; mucosal barrier; TLR4
• ISSN: 1791-2997; 1791-3004; 1791-3004
• DOI: 10.3892/mmr.2022.12684

Hirschsprung‑associated enterocolitis (HAEC) is characterized by intestinal mucosal damage and an imbalance in the intestinal microbiota. Recent studies have indicated that the TLR4/p‑p38/NF‑κB signaling pathway in the intestine is of great importance to intestinal mucosal integrity. The present study aimed to investigate the role of TLR4/phosphorylated (p‑)38/NF‑κB signaling in the pathogenesis of HAEC in JM83‑infected endothelin receptor B (Ednrb) mice. Ednrb mice were infected with JM83 by oral gavage to establish the HAEC model. Wild‑type and Ednrb mice were randomly divided into uninfected and E. coli groups. The role of TLR4/p‑p38/NF‑κB signaling was further evaluated by and analyses. The activation of the TLR4/p‑p38/NF‑κB signaling pathway induced by JM83 resulted in HAEC in Ednrb mice, which was evidenced by a significant increase in the expression of TNF‑α, TGF‑β and IL‑10, and a decreased density of F‑actin protein expression. TLR4 knockdown reduced the severity of enterocolitis and attenuated the expression of IL‑10, TNF‑α and TGF‑β, whilst increasing the density of F‑actin protein in Ednrb mice after infection. These results indicated that E. coli JM83 activates TLR4/p‑p38/NF‑κB signaling in Ednrb to promote the development of HAEC. Thus, inhibition of this signaling pathway may benefit the treatment and prevention of HAEC.