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
Abstract
BACKGROUND

Ulcerative colitis (UC) is a chronic, nonspecific intestinal inflammatory disease with undefined pathogenesis. Non-SMC condensin I complex subunit D2 (NCAPD2) and non-SMC condensin II complex subunit D3 (NCAPD3) play pivotal roles in chromosome assembly and segregation during both mitosis and meiosis. To date, there has been no relevant report about the functional role of NCAPD2 and NCAPD3 in UC.

AIM

To determine the level of NCAPD2/3 in intestinal mucosa and explore the mechanisms of NCAPD2/3 in UC.

METHODS

Levels of NCAPD2/3 in intestinal tissue were detected in 30 UC patients and 30 healthy individuals with in situ hybridization (ISH). In vitro, NCM60 cells were divided into the NC group, model group, si-NCAPD2 group, si-NCAPD3 group and si-NCAPD2+si-NCAPD3 group. Inflammatory cytokines were measured by ELISA, IKK and NF-κB were evaluated by western blot, and IKK nucleation and NF-κB volume were analyzed by immunofluorescence assay.

RESULTS

Compared with expression in healthy individuals, NCAPD2 and NCAPD3 expression in intestinal tissue was significantly upregulated (P < 0.001) in UC patients. Compared with levels in the model group, IL-1β, IL-6 and TNF-α in the si-NCAPD2, si-NCAPD3 and si-NCAPD2+si-NCAPD3 groups were significantly downregulated (P < 0.01). IKK and NF-κB protein expression in the si-NCAPD2, si-NCAPD3 and si-NCAPD2+si-NCAPD3 groups was significantly decreased (P < 0.01). Moreover, IKK nucleation and NF-κB volume were suppressed upon si-NCAPD2, si-NCAPD3 and si-NCAPD2+ si-NCAPD3 transfection.

CONCLUSION

NCAPD2/3 is highly expressed in the intestinal mucosa of patients with active UC. Overexpression of NCAPD2/3 promotes the release of pro-inflammatory cytokines by modulating the IKK/NF-κB signaling pathway.

Keywords: Non-SMC condensin I complex subunit D2; Non-SMC condensin II complex subunit D3; Ulcerative colitis; Inflammation; IKK/NF-κB; Pathway

Core tip: In this study, non-SMC condensin I complex subunit D2 (NCAPD2) and non-SMC condensin II complex subunit D3 (NCAPD3) expression levels have been confirmed to be significantly up-regulated in the intestinal mucosa of patients with active UC. In vitro, the data suggested that silencing NACPD2 and NACPD3 could depress the expression of IL-1β, IL-6 and TNF-α. Further, knockdown of NACPD2 and NACPD3 could remarkably suppress IKK nucleation and NF-κB volume. These results suggest that NACPD2 and NACPD3 are over-expressed in the intestinal mucosa of patients with UC, and overexpression of NCAPD2/3 promotes the release of pro-inflammatory cytokines by modulating the IKK/NF-κB signaling pathway.