Published online Sep 21, 2021. doi: 10.3748/wjg.v27.i35.5946
Peer-review started: March 5, 2021
First decision: April 5, 2021
Revised: April 7, 2021
Accepted: August 10, 2021
Article in press: August 10, 2021
Published online: September 21, 2021
Currently, the etiology and pathogenesis of Crohn’s disease (CD) are not completely known, which makes it incurable. It is urgent to reveal the pathophysiological mechanism of CD and investigate new therapeutic targets.
To explore a potential therapeutic target for CD and verify its role in the CD pathological mechanism.
In this study, we attempted to find a potential therapeutic target for CD and verify its role in the CD pathological mechanism in vitro.
Proteomics was implemented to quantify the protein profile in the plasma of CD patients. Among the differentially expressed proteins, a hub gene that could regulate the immune response was selected for further study. The expression of the selected hub gene in the inflamed intestinal mucosa was verified by immunohistochemical staining. In vitro, the effects of the hub gene on the expression of proinflammatory cytokines and the NF-κB signalling pathway were evaluated by ELISA, qRT-PCR, and Western blot analysis.
Fibrinogen-like protein 1 (FGL1), as a hub gene of the differentially expressed proteins, was confirmed to be markedly upregulated in the plasma and intestinal mucosa of CD patients. Silencing FGL1 downregulated the levels of the proinflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α. Furthermore, FGL1 knockdown repressed the mRNA expression of NF-κB and the protein levels of IKKα, IKKβ, p-IKKα/β, p-IκBα, and p-p65. Overexpression of FGL1 enhanced these results.
FGL1 may promote intestinal inflammation modulated by the canonical NF-κB signalling pathway and has the potential to be a therapeutic target for CD.
Our findings indicate a critical role of FGL1 in the onset and progression of CD, which may serve as a potential prognostic biomarker and therapeutic target for CD.