Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2021; 27(35): 5946-5957
Published online Sep 21, 2021. doi: 10.3748/wjg.v27.i35.5946
Proteomics identifies a novel role of fibrinogen-like protein 1 in Crohn’s disease
Xue-Liang Sun, Li-Chao Qiao, Jing Gong, Ke Wen, Zhi-Zhong Xu, Bo-Lin Yang
Xue-Liang Sun, Li-Chao Qiao, Jing Gong, Bo-Lin Yang, First Clinical Medical College, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Xue-Liang Sun, Ke Wen, Zhi-Zhong Xu, Department of Colorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215000, Jiangsu Province, China
Bo-Lin Yang, Department of Colorectal Surgery, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Author contributions: Sun XL and Yang BL contributed to designing the study; Sun XL, Qiao LC and Gong J contributed to performing the experiments; Wen K and Xu ZZ contributed to sample collection and statistical analysis; Sun XL and Qiao LC contributed to manuscript drafting; all authors made critical revisions to the manuscript and approved the final version of the article to be published.
Supported by National Natural Science Foundation of China, No. 82074431; The Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Subject of Academic Priority Discipline of Jiangsu Higher Education Institutions, No. ZYX03KF034; and Suzhou Municipal Science and Technology Bureau, No. SYSD2020253 and No. SS202085.
Institutional review board statement: The study was approved by the Ethics Committee of the Affiliated Hospital of Nanjing University of Chinese Medicine (2018NL-171-02).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Bo-Lin Yang, MD, Chief Doctor, First Clinical Medical College, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, China.
Received: March 5, 2021
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
Research background

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.

Research motivation

To explore a potential therapeutic target for CD and verify its role in the CD pathological mechanism.

Research objectives

In this study, we attempted to find a potential therapeutic target for CD and verify its role in the CD pathological mechanism in vitro.

Research methods

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.

Research results

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.

Research conclusions

FGL1 may promote intestinal inflammation modulated by the canonical NF-κB signalling pathway and has the potential to be a therapeutic target for CD.

Research perspectives

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.