Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2019; 25(47): 6813-6822
Published online Dec 21, 2019. doi: 10.3748/wjg.v25.i47.6813
Non-SMC condensin I complex subunit D2 and non-SMC condensin II complex subunit D3 induces inflammation via the IKK/NF-κB pathway in ulcerative colitis
Chang-Wen Yuan, Xue-Liang Sun, Li-Chao Qiao, Hai-Xia Xu, Ping Zhu, Hong-Jin Chen, Bo-Lin Yang
Chang-Wen Yuan, Department of Neurology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Xue-Liang Sun, Li-Chao Qiao, Hai-Xia Xu, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Ping Zhu, Hong-Jin Chen, Bo-Lin Yang, Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Author contributions: Yuan CW, Yang BL Qiao LC, Xu HX and Zhu P studied concept, analyzed and interpreted data, prepared manuscript and revised important intellectual content; Sun XL and Chen HJ analyzed and interpreted data and clinical material support; Qiao LC, Xu HX and Zhu P analyzed and interpreted data.
Supported by National Natural Science Foundation of China, No. 81673973; Natural Science Foundation of Jiangsu Province, China, No. BK20161577; and the Developing Program for High-level Academic Talent from Jiangsu Hospital of Chinese Medicine, No. y2018rc16.
Institutional review board statement: Approved by the ethics committee of the Affiliated Hospital of Nanjing University of Chinese Medicine (2018NL-170-02).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Bo-Lin Yang, MD, Chief Doctor, Professor, Surgeon, Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, China. yfy0051@njucm.edu.cn
Telephone: +86-18602519077
Received: September 23, 2019
Peer-review started: September 23, 2019
First decision: November 4, 2019
Revised: November 20, 2019
Accepted: December 7, 2019
Article in press: December 7, 2019
Published online: December 21, 2019
Processing time: 88 Days and 1.6 Hours
ARTICLE HIGHLIGHTS
Research background

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease affecting the colon, and the precise molecular mechanisms are undefined. To date, some evidence suggested that non-SMC condensin I complex subunit D2 (NCAPD2) and non-SMC condensin II complex subunit D3 (NCAPD3) play important roles in mitosis and meiosis. Recently, it has been suggested in the literature that subunits of condensing I and condensin II are involved in human cancers, included colorectal cancer. Schuster et al[12] has reported that NCAPD3 down-regulates the transcription of genes that encode amino acid transporters (SLC7A5 and SLC3A2) to promote bacterial autophagy by colonic epithelial cells.

Research motivation

To date, there are few studies regarding the correlation of NCAPD2 and NCAPD3 with human diseases, especially in UC. We hypothesize that NCAPD2/3 can also be a potential pathogenic or diagnostic target for ulcerative colitis, and could be used as a new therapeutic target in the future.

Research objectives

In this study, we identified high expression of NCAPD2/3 in the intestinal mucosa of patients with UC. We also analyzed the NCM60 colonic epithelial cell line expressing inducible siRNAs targeting NCAPD2/3, and for the first time, we found that NCAPD2/3 may induce inflammation via the IKK/NF-κB pathway in UC. These findings reveal an important role for NCAPD2/3 in UC, thus providing a potential new direction for UC research.

Research methods

We used in situ hybridization (ISH) to measure levels of NCAPD2/3 in intestinal tissue from patients with UC and healthy individuals. In vitro, the inflammatory cytokines IKK and NF-κB were evaluated by ELISA, WB and immunofluorescence assay with NCM60 cells expressing small hairpin RNAs against NCAPD2/3.

Research results

In this study, we found that NCAPD2 and NCAPD3 protein expression in intestinal tissue was significantly higher in UC patients than in healthy people. We also found that knockdown of NACPD2/3 in normal colonic epithelial cells (NCM460 cell) resulted in a significant downregulation of IL-1β, IL-6 and TNF-α, possibly by regulating the IKK/NF-κB signaling pathway.

Research conclusions

Levels of NCAPD2/3 proteins are increased in patients with active UC. NCAPD2/3 promote the release of inflammatory cytokines such as IL-1β, IL-6 and TNF-α, which modulate the IKK/NF-κB signaling pathway.

Research perspectives

Our findings indicate a critical role for NCAPD2/3 in the onset and progression of inflammatory bowel disease, as well as strategies to decrease NCAPD2/3 levels that might inhibit inflammation in patients with active UC.