Plakoglobin and High-Mobility Group Box 1 Mediate Intestinal Epithelial Cell Apoptosis Induced by Clostridioides difficile TcdB
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
Author(s)
Related Research Unit(s)
Detail(s)
Original language | English |
---|---|
Number of pages | 18 |
Journal / Publication | mBio |
Volume | 13 |
Issue number | 5 |
Online published | 31 Aug 2022 |
Publication status | Published - Oct 2022 |
Link(s)
DOI | DOI |
---|---|
Attachment(s) | Documents
Publisher's Copyright Statement
|
Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85140856419&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(c1c85590-fe2a-4329-8bb8-f2b9eae083af).html |
Abstract
Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated intestinal disease, resulting in severe diarrhea and fatal pseudomembranous colitis. TcdB, one of the essential virulence factors secreted by this bacterium, induces host cell apoptosis through a poorly understood mechanism. Here, we performed an RNA interference (RNAi) screen customized to Caco-2 cells, a cell line model of the intestinal epithelium, to discover host factors involved in TcdB-induced apoptosis. We identified plakoglobin, also known as junction plakoglobin (JUP) or γ-catenin, a member of the catenin family, as a novel host factor and a previously known cell death-related chromatin factor, high-mobility group box 1 (HMGB1). Disruption of those host factors by RNAi and CRISPR resulted in resistance of cells to TcdB-mediated and mitochondrion-dependent apoptosis. JUP was redistributed from adherens junctions to the mitochondria and colocalized with the antiapoptotic factor Bcl-XL. JUP proteins could permeabilize the mitochondrial membrane, resulting in the release of cytochrome c. Our results reveal a novel role of JUP in targeting the mitochondria to promote the mitochondrial apoptotic pathway. Treatment with glycyrrhizin, an HMGB1 inhibitor, resulted in significantly increased resistance to TcdB-induced epithelial damage in cultured cells and a mouse ligated colon loop model. These findings demonstrate the critical roles of JUP and HMGB1 in TcdB-induced epithelial cell apoptosis. © 2022 Li et al.
Research Area(s)
- C. difficile, TcdB, apoptosis, JUP, HMGB1, RNAi screen, TOXIN-B, BARRIER FUNCTION, PROTEIN, INFECTION, INFLAMMATION, IDENTIFICATION, MITOCHONDRIA, RECEPTOR, STRAIN, TARGET
Citation Format(s)
Plakoglobin and High-Mobility Group Box 1 Mediate Intestinal Epithelial Cell Apoptosis Induced by Clostridioides difficile TcdB. / Li, Yingxue; Xu, Wei; Ren, Yutian et al.
In: mBio, Vol. 13, No. 5, 10.2022.
In: mBio, Vol. 13, No. 5, 10.2022.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
Download Statistics
No data available