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Zbtb14 Promotes Non-Alcoholic Fatty Liver Disease-Associated Fibrosis in Gerbils via the β-Catenin Pathway
Guocan Chen1, Xiaobing Wang2, Yongfen Zhu3
1Center for Drug Safety Evaluation, Hangzhou Medical College, 310013 Hangzhou, Zhejiang, China.
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.
Insights
Zinc Finger and BTB Domain Containing 14 (Zbtb14) drives non-alcoholic fatty liver disease fibrosis by regulating hepatic stellate cell activation. This study identifies Zbtb14 as a potential therapeutic target for treating liver fibrosis in NAFLD.
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition lacking approved treatments.
- Liver fibrosis is a key indicator of drug efficacy in NAFLD, necessitating research into its mechanisms and therapeutic targets.
Purpose of the Study:
- To investigate the mechanisms underlying NAFLD-associated liver fibrosis.
- To identify potential therapeutic targets for NAFLD.
Main Methods:
- A gerbil model of NAFLD-associated fibrosis was established using a high-fat, high-cholesterol diet.
- Liver injury and fibrosis were assessed via histological staining and biochemical assays (ALT, AST, Hyp).
- Differential gene expression was analyzed using mRNA sequencing, and cell viability was tested using the Cell Counting Kit-8.
Main Results:
- The gerbil model exhibited liver injury and fibrosis, with elevated ALT, AST, and Hyp levels.
- Differentially expressed genes were primarily associated with negative regulation of hemopoiesis, response to interleukin-1, and granulocyte migration.
- Zinc Finger and BTB Domain Containing 14 (Zbtb14) was found to be upregulated in fibrotic liver tissues and hepatic stellate cells (HSCs), regulating HSC activation via the β-catenin pathway.
Conclusions:
- Zbtb14 plays a novel role in regulating NAFLD-associated fibrosis through the β-catenin pathway.
- Zbtb14 represents a potential therapeutic target for NAFLD treatment.
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