Liu H, Sun ZY, Jiang H, Li XD, Jiang YQ, Liu P, Huang WH, Lv QY, Zhang XL, Li RK. Transcriptome sequencing and experiments reveal the effect of formyl peptide receptor 2 on liver homeostasis. World J Gastroenterol 2023; 29(24): 3793-3806 [PMID: 37426322 DOI: 10.3748/wjg.v29.i24.3793]
Corresponding Author of This Article
Rong-Kuan Li, MD, Chief Doctor, Department of Infectious Diseases, Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian 116000, Liaoning Province, China. dalianlrk1@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
Hui Liu, Department of Gastroenterology, Second Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China
Ze-Yu Sun, Hua Jiang, Yong-Qiang Jiang, Peng Liu, Wen-Hua Huang, Qing-Yu Lv, Xiang-Lilan Zhang, State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China
Xu-Dong Li, Microbiology Teaching and Research Office, Anhui Medical University, Hefei 230032, Anhui Province, China
Rong-Kuan Li, Department of Infectious Diseases, Second Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China
Author contributions: Li RK designed the research; Liu H wrote the manuscript; Jiang H, Sun ZY, and Li XD conducted experiments; Liu P, Huang WH, and Lv QY analyzed the data and drew pictures; Jiang YQ and Zhang XL revised the manuscript content; all authors approved the final version of the article.
Supported bythe State Key Laboratory of Pathogen and Biosecurity, No. SKLPBS2119 and SKLPBS2212; and the Medical Science Research Project of Dalian, No. 2112015.
Institutional animal care and use committee statement: The animal study was reviewed and approved by the animal center of the Academy of Military Medical Sciences. The protocol for animal handling and experiment was approved by the Institutional Review Board of Academy of Military Medical Science (No: IACUC-DWZX-2022-052).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, PRJNA923726.
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 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rong-Kuan Li, MD, Chief Doctor, Department of Infectious Diseases, Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian 116000, Liaoning Province, China. dalianlrk1@163.com
Received: April 18, 2023 Peer-review started: April 18, 2023 First decision: April 26, 2023 Revised: May 4, 2023 Accepted: May 22, 2023 Article in press: May 22, 2023 Published online: June 28, 2023 Processing time: 71 Days and 1 Hours
ARTICLE HIGHLIGHTS
Research background
Formyl peptide receptor 2 (Fpr2) plays an important role in host’s defense and inflammatory response, as it can help the body control bacterial infections. Studies have found that in Fpr2-/- mice, the liver is the most severely damaged target organ in bloodstream infections. However, the reason for this is unclear.
Research motivation
To verify the role of Fpr2 in liver homeostasis, to provide new clues for the decreased ability of the liver to clear bacteria after Fpr2 deficiency, and to provide new ideas for future drug research and development.
Research objectives
To investigate the role of Fpr2 in liver homeostasis.
Research methods
The differentially expressed genes (DEGs) in Fpr2-/- and wild-type (WT) mice were determined by transcriptome sequencing, and the biological functions of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Quantitative real-time polymerase chain reaction (qRT PCR) and western blot (WB) were used to further validate the expression levels of differential genes. The Cell Counting Kit-8 assay was used to study cell proliferation. A cell cycle detection kit was used to measure the distribution of cell cycles. Luminex assay was used to analyze cytokine levels in the liver. A fully automated biochemical analyzer was used to detect the levels of serum biochemical indicators and C-reactive protein in WT and Fpr2-/- mice. The number of neutrophils in the liver was detected by flow cytometry. The histopathology of the liver was analyzed by hematoxylin-eosin staining.
Research results
Transcriptome sequencing showed that, compared with WT group, 445 genes in the liver of Fpr2-/- mice had significant changes in the expression level, including 325 upregulated genes and 120 downregulated genes. The functional enrichment analysis of GO and KEGG indicated that these DEGs were mainly related to cell cycle. qRT-PCR validated that after Fpr2 deletion, the expression levels of CycA, CycB1, Cdc20, and Cdc25c genes were upregulated. Both qRT-PCR and WB confirmed a decrease in the expression of CDK1. WRW4 (an antagonist of Fpr2) could inhibit the proliferation of HepG2 cells in a concentration dependent manner. The levels of serum alanine aminotransferase levels increased in Fpr2-/- mice with statistical significance. Luminex assay measurements showed that the expression levels of interleukin (IL)-10, IL-18, and CXCL-1 were significantly reduced in the liver of Fpr2-/- mice.
Research conclusions
Fpr2 may exert a protective effect on the liver by participating in the regulation of cell cycle and proliferation, as well as affecting the expression of IL-10 and CXCL-1.
Research perspectives
Fpr2 plays an important role in maintaining liver homeostasis, and its agonist may be a potential drug against bacterial infection.
