2. Academic Validation
  3. Autotaxin promotes the degradation of the mucus layer by inhibiting autophagy in mouse colitis

Autotaxin promotes the degradation of the mucus layer by inhibiting autophagy in mouse colitis

  • Mol Immunol. 2023 Jun 23;160:44-54. doi: 10.1016/j.molimm.2023.06.002.
Xiaoyan Chen 1,  Hui Zhang 2,  Xiaojiang Zhou 3,  Yunwu Wang 3,  Wenjie Shi 4
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China; The State Key Laboratory of Digestive Disease, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 2 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 3 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 4 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address: Shiwenjie@alumni.hust.edu.cn.
PMID: 37356325 DOI: 10.1016/j.molimm.2023.06.002
Abstract

Autotaxin (ATX or ENPP2) is an autocrine Enzyme associated with the metabolism of various Phospholipids. ATX has recently been identified as a regulatory factor in immune-related and inflammation-associated diseases, such as inflammatory bowel disease, but the exact mechanism is unclear. Here, we treated mice with recombinant ATX protein or an ATX inhibitor to investigate the effect of ATX on colitis in mice and the underlying mechanism. In a mouse model of colitis, ATX expression was increased, Autophagy was impaired, and the mucus barrier was disrupted. Recombinant ATX protein promoted intestinal inflammation, inhibited Autophagy, and disrupted the mucus barrier, while an ATX inhibitor had the opposite effect. Next, we treated mice that received ATX with an Autophagy activator and an adenosine 5'-monophosphate-activated protein kinase (AMPK) agonist. We observed that Autophagy activator and AMPK agonist could repair the mucus barrier and alleviate intestinal inflammation in ATX-treated mice. In vitro, we obtained consistent results. Thus, we concluded that ATX could inhibit Autophagy through the AMPK pathway, which consequently disordered the mucus barrier and aggravated intestinal inflammation.

Keywords

AMPK; Autophagy; Autotaxin; Mucus barrier; Ulcerative colitis.

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