Research Paper Volume 14, Issue 5 pp 2287—2303
MafK accelerates Salmonella mucosal infection through caspase-3 activation
- 1 Department of Basic Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin, China
- 2 Department of Comparative and Experimental Medicine, Nagoya City University Graduate 24 School of Medical Sciences, Aichi 467-8601, Nagoya, Japan
- 3 Institute of Basic Medical Sciences and Laboratory Animal Resource Center, University of Tsukuba, Ibaraki 305-8575, Tsukuba, Japan
- 4 Department of Endocrinology and Metabolism, The Second Hospital of Jilin University, Changchun 130000, Jilin, China
Received: August 23, 2021 Accepted: February 28, 2022 Published: March 8, 2022
https://doi.org/10.18632/aging.203938How to Cite
Copyright: © 2022 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Gastrointestinal homeostasis is critical for maintaining host health, and is affected by many factors. A recent report showed that Musculoaponeurotic fibrosarcoma K (MafK) expression is increased in patients that have ulcerative colitis (UC). Even so, MafK’s significance in sustaining intestinal homeostasis has not been investigated. In this research, MafK overexpressing transgenic (MafK Tg) mice were found to be more susceptible to infection with Salmonella on the mucosa than the wild-type (WT) mice. Following Salmonella oral infection, MafK Tg mice suffered higher mortality and a lot more weight loss, damage to the intestines, and inflammation in the intestines than WT mice. MafK Tg mice were also unable to control Salmonella colonization and dissemination. In vivo data showed that increased MafK expression promoted epithelial cell apoptosis which was further confirmed by in vitro data. The rapid cleavage of caspase-3 in epithelial cells contributed to Salmonella dissemination and inflammation initiation. This study reveals that MafK participates in Salmonella pathogenesis acceleration by increasing caspase-3 activation.
Abbreviations
MafK: Musculoaponeurotic fibrosarcoma K; MafK Tg: MafK overexpressing transgenic; WT: Wild-type; IECs: Intestinal epithelial cells; CD: Crohn’s disease; UC: Ulcerative colitis; IBD: Inflammatory bowel disease; Maf: Macrophage-activating factor; CFU: Colony-forming unit; H&E: Hematoxylin and eosin; MPO: Myeloperoxidase; CDS: Coding sequence; siRNA: Small-interfering RNA; DMEM: Dulbecco’s modified eagle’s medium; FBS: Fetal bovine serum; IL-6: Interleukin-6; IL-1β: Interleukin-1β; TNF-α: Tumor necrosis factor-α; INF-γ: Interferon-γ; L-10: Interleukin-10; Cox-2: Cyclooxygenase-2; iNOS: Inducible nitric oxide synthase; MLNs: Mesenteric lymph nodes; ZO-1: Zonula occludens-1; TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling.