Exploration and verification of COVID-19-related hub genes in liver physiological and pathological regeneration

Jihang Shi; Guangya Li; Xiandun Yuan; Yafei Wang; Ming Gong; Chonghui Li; Xinlan Ge; Shichun Lu

doi:10.3389/fbioe.2023.1135997

Exploration and verification of COVID-19-related hub genes in liver physiological and pathological regeneration

Front Bioeng Biotechnol. 2023 Feb 23:11:1135997. doi: 10.3389/fbioe.2023.1135997. eCollection 2023.

Authors

Jihang Shi^{1

2

3}, Guangya Li^{4

5}, Xiandun Yuan⁶, Yafei Wang^{1

2

3}, Ming Gong^{1

2

3}, Chonghui Li^{2

3}, Xinlan Ge^{2

3}, Shichun Lu^{2

3}

Affiliations

¹ Medical School of Chinese People's Liberation Army (PLA), Beijing, China.
² Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.
³ Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, China.
⁴ MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
⁵ Peking University-Tsinghua University-National Institute of Biological Science Joint Graduate Program, College of Life Science, Peking University, Beijing, China.
⁶ Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China.

Abstract

Objectives An acute injury is often accompanied by tissue regeneration. In this process, epithelial cells show a tendency of cell proliferation under the induction of injury stress, inflammatory factors, and other factors, accompanied by a temporary decline of cellular function. Regulating this regenerative process and avoiding chronic injury is a concern of regenerative medicine. The severe coronavirus disease 2019 (COVID-19) has posed a significant threat to people's health caused by the coronavirus. Acute liver failure (ALF) is a clinical syndrome resulting from rapid liver dysfunction with a fatal outcome. We hope to analyze the two diseases together to find a way for acute failure treatment. Methods COVID-19 dataset (GSE180226) and ALF dataset (GSE38941) were downloaded from the Gene Expression Omnibus (GEO) database, and the "Deseq2" package and "limma" package were used to identify differentially expressed genes (DEGs). Common DEGs were used for hub genes exploration, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to verify the role of hub genes in liver regeneration during in vitro expansion of liver cells and a CCl4-induced ALF mice model. Results: The common gene analysis of the COVID-19 and ALF databases revealed 15 hub genes from 418 common DEGs. These hub genes, including CDC20, were related to cell proliferation and mitosis regulation, reflecting the consistent tissue regeneration change after the injury. Furthermore, hub genes were verified in vitro expansion of liver cells and in vivo ALF model. On this basis, the potential therapeutic small molecule of ALF was found by targeting the hub gene CDC20. Conclusion We have identified hub genes for epithelial cell regeneration under acute injury conditions and explored a new small molecule Apcin for liver function maintenance and ALF treatment. These findings may provide new approaches and ideas for treating COVID-19 patients with ALF.

Keywords: ALF; Apcin; COVID-19; cdc20; liver regeneration.