Published online Dec 21, 2019. doi: 10.3748/wjg.v25.i47.6813
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
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 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.
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.
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.
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.
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.
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.
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.