The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitocho
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RESEARCH ARTICLE
Open Access
The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondriadependent pathway Jinhua Liang1†, Yongzhong Ning2†, Li Dong3, Xiufeng Ma3, Shu Li1, Heran Yang1, Qi Li1, Ling Chen4, Lingjuan Gao5 and Yanmin Xu3*
Abstract Background: Clostridioides (formerly Clostridium) difficile infection is the leading cause of antibiotic-associated colitis. Studies have demonstrated that C. difficile toxin A (TcdA) can cause apoptosis of many human cell types. The purpose of this study was to investigate the relationships among exposure to TcdA, the role of the receptor for the globular heads of C1q (gC1qR) gene and the underlying intracellular apoptotic mechanism in human colonic epithelial cells (NCM 460). In this study, gC1qR expression was examined using real-time polymerase chain reaction (PCR), western blotting and immunohistochemical staining. Cell viability was assessed by the water-soluble tetrazolium salt (WST-1) assay, and cell apoptosis was assessed by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Mitochondrial function was assessed based on reactive oxygen species (ROS) generation, changes in the mitochondrial membrane potential (ΔΨm) and the content of ATP. Results: Our study demonstrated that increasing the concentration of TcdA from 10 ng/ml to 20 ng/ml inhibited cell viability and induced cell apoptosis (p < 0.01). Moreover, the TcdA-induced gC1qR expression and enhanced expression of gC1qR caused mitochondrial dysfunction (including production of ROS and decreases in the ΔΨm and the content of ATP) and cell apoptosis. However, silencing of the gC1qR gene reversed TcdA-induced cell apoptosis and mitochondrial dysfunction. Conclusion: These data support a mechanism by which gC1qR plays a crucial role in TcdA-induced apoptosis of human colonic epithelial cells in a mitochondria-dependent manner. Keywords: Clostridium difficile, TcdA, gC1qR, Mitochondrial function, apoptosis
* Correspondence: [email protected] † Jinhua Liang and Yongzhong Ning contributed equally to this work. 3 Three Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical College, Tongxiang Road, Aimin District, Mudanjiang 157000, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is
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