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

Abstract

BACKGROUNDUlcerative 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.AIMTo determine the level of NCAPD2/3 in intestinal mucosa and explore the mechanisms of NCAPD2/3 in UC.METHODSLevels 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.RESULTSCompared 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.CONCLUSIONNCAPD2/3 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.

High Throughput Genetic Characterisation of Caucasian Patients Affected by Multi-Drug Resistant Rheumatoid or Psoriatic Arthritis

“…In detail, patient SN3 has the variant c.1712A>C; p.His571Pro within the NCAPD3 gene, while subject SN5 carries the variant c.860C>G; p.Pro287Arg within NCAPD2 . Both genes have a role in releasing pro-inflammatory cytokine and modulating the NF-κB signalling pathway [ 37 ].…”

Comparison of the Effects of Essential Oil Obtained from the Crude and Bran-Processed Atractylodes lancea on Lipopolysaccharide-Induced Inflammatory Injury of Human Colonic Epithelial Cells by Downregulating the IKK/NF-κB Signaling Pathway

“…After stimulation, I κ B kinase (IKK) becomes phosphorylated, resulting in the phosphorylation of I κ B, which dissociates from NF- κ B and enters the nucleus to regulate the secretion and expression of inflammatory factors. The activation of IKK/NF- κ B, which is an essential cause of severe inflammation [ 35 , 36 ], increases the secretion of the proinflammatory cytokines and induces inflammatory reactions [ 37 , 38 ].…”

Construction of prognostic predictor by comprehensive analyzing alternative splicing events for colon adenocarcinoma

“…Gan et al [ 27 ] reported that KIF2C is a target gene of miR-325-3p, which has been shown to be a tumor suppressor in non-small-cell lung cancer. Yuan et al [ 28 ] reported that over-expression of NCAPD2/3 promotes the release of pro-inflammatory cytokines by modulating the IKK/NF-κB signaling pathway. Han et al [ 29 ] reported that TRAIP is crucial in early mitotic progression and chromosome alignment defects in the metaphase.…”