FBP1 as a key regulator of focal adhesion kinase-mediated hepatic stellate cell activation: Multi-omics and experimental validation

doi:10.3748/wjg.v31.i28.107361

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Jul 28, 2025; 31(28): 107361
Published online Jul 28, 2025. doi: 10.3748/wjg.v31.i28.107361

FBP1 as a key regulator of focal adhesion kinase-mediated hepatic stellate cell activation: Multi-omics and experimental validation

Hua-Yue Wu, Lu Han, Tao Ran, Yong Sun, Qing-Xiu Zhang, Tao Huang, Gao-Liang Zou, Ya Zhang, Yu-Mei Zhou, Guo-Yuan Lin, Shao-Jie Chen, Jing-Lin Wang, Chen Pan, Fan Lu, Hong-Fei Pu, Xue-Ke Zhao

Hua-Yue Wu, Lu Han, Tao Ran, Qing-Xiu Zhang, Tao Huang, Gao-Liang Zou, Ya Zhang, Yu-Mei Zhou, Guo-Yuan Lin, Xue-Ke Zhao, Department of Infectious Disease, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China

Yong Sun, Shao-Jie Chen, Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China

Jing-Lin Wang, Department of Gastroenterology, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou Province, China

Chen Pan, Department of Gastroenterology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China

Fan Lu, Department of Obstetrics, The Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou Province, China

Hong-Fei Pu, Department of Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou Province, China

Co-first authors: Hua-Yue Wu and Lu Han.

Author contributions: Wu HY performed the majority of the experiments, and wrote the initial draft of the manuscript; Han L and Zhou YM participated in the cell experiments; Zhang QX, Zhang Y, and Ran T were involved in the animal experiments; Huang T, Zou GL, Sun Y, Chen SJ, and Lu F conducted the statistical analyses; Pan C, Lin GY, Pu HF, and Wang JL were responsible for the data organization; Zhao XK proofread the manuscript; All authors read and approved the final manuscript. Wu HY and Han L contributed equally to this study as co-first authors.

Supported by the Science and Technology Program of the Guizhou Province, No. [2021]094; National Natural Science Foundation of China, No. 82060116 and No. 82260129; Guizhou Provincial Science and Technology Program, No. QKHJC-ZK[2023]214; and Doctoral Research Start-up Fund Project of Guizhou Medical University, No. gyfybsky[2021]63.

Institutional review board statement: All procedures were approved by the Clinical Trial Ethics Committee of the Affiliated Hospital of Guizhou Medical University (Approval 2022, Ethics Review No. 023).

Institutional animal care and use committee statement: All experiments, including the mouse experiments, were conducted in compliance with relevant ethical regulations and were approved by the Ethics Committee of Guizhou Medical University (Approval No. 2403086).

Conflict-of-interest statement: The authors have no conflicts of interest to declare.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Raw data have been deposited in the National Center for Biotechnology Information (NCBI) under the BioProject number PRJNA1226283. Proteomics sequencing data have been uploaded to the iProX database, project ID: IPX0011179000.

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: Xue-Ke Zhao, MD, Department of Infectious Disease, The Affiliated Hospital of Guizhou Medical University, No. 9 Beijing Road, Guiyang 550004, Guizhou Province, China. zhaoxueke1@163.com

Received: March 21, 2025
Revised: April 29, 2025
Accepted: June 19, 2025
Published online: July 28, 2025
Processing time: 125 Days and 1.6 Hours

Core Tip

Core Tip: In this study, we showed that focal adhesion kinase (FAK) inhibitors suppress hepatic stellate cell (HSC) activation and aerobic glycolysis, thereby alleviating liver fibrosis (LF). Fructose-1, 6-bisphosphatase 1 (FBP1) inhibits HSC activation and migration by regulating aerobic glycolysis. FAK can affect the expression of FBP1. Therefore, both FAK and FBP1 may serve as potential therapeutic targets for LF.