IMR Press / FBL / Volume 28 / Issue 9 / DOI: 10.31083/j.fbl2809205
Open Access Original Research
Zbtb14 Promotes Non-Alcoholic Fatty Liver Disease-Associated Fibrosis in Gerbils via the β-Catenin Pathway
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1 Center for Drug Safety Evaluation, Hangzhou Medical College, 310013 Hangzhou, Zhejiang, China
2 Medical School of Jinhua Polytechnic, 321016 Jinhua, Zhejiang, China
3 Department of Hepatology and Infection, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, 310020 Hangzhou, Zhejiang, China
4 High Level Bio-safety Laboratory, Hangzhou Medical College, 310013 Hangzhou, Zhejiang, China
*Correspondence: (Xiaofeng Chu)
Front. Biosci. (Landmark Ed) 2023, 28(9), 205;
Submitted: 26 November 2022 | Revised: 16 March 2023 | Accepted: 23 March 2023 | Published: 15 September 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Non-alcoholic fatty liver disease (NAFLD) is a popular chronic liver disorder with high morbidity and with no approved therapeutic drugs. Fibrosis is a crucial drug efficacy indicator for NAFLD. Thus, investigating the mechanisms of NAFLD-associated fibrosis and exploring effective therapeutic targets is imperative. Methods: Gerbil NAFLD-associated fibrosis model was constructed by feeding a high-fat and high-cholesterol diet. The hematoxylin and eosin staining and the alanine transaminase (ALT) and aspartate transaminase (AST) assays were used to determine liver tissue injury. Masson staining and hydroxyproline (Hyp) level determination were used to assess liver fibrosis. High-throughput mRNA sequencing was used to screen differentially expressed genes in the NAFLD-associated fibrosis model. Cell Counting Kit-8 was utilized to test cell viability. Results: Liver injury and fibrosis were observed in the gerbil NAFLD-associated fibrosis model with increased ALT, AST, and Hyp levels. The screened differentially expressed genes were mainly enriched in “negative regulation of hemopoiesis”, “response to interleukin-1”, and “granulocyte migration”. Zinc Finger and BTB Domain Containing 14 (Zbtb14) was upregulated in liver tissues of the gerbil NAFLD-associated fibrosis model, patients with liver fibrosis, and hepatic stellate cells (HSCs). Additionally, Zbtb14 regulated primary HSCs activation via the β-catenin pathway. Conclusions: Zbtb14 regulated NAFLD-associated fibrosis via the β-catenin pathway, for the first time, and it serves as the probable target for NAFLD therapy.

non-alcoholic fatty liver disease
hepatic stellate cells
31970511/National Natural Science Foundation of China
LGD20C040003/Zhejiang province commonweal projects
Fig. 1.
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