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Identification and validation of immune related core transcription factors GTF2I in NAFLD
Minbo Zhang1, Yu Zhang1, Xiaoxiao Jiao1
1Department of Gastroenterology and Hepatology, Tongji Hospital of Tongji University, Shanghai, China.
Background:
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide that endangers human health. Transcription factors (TFs) have gradually become hot spots for drug development in NAFLD for their impacts on metabolism. However, the specific TFs that regulate immune response in the development of NAFLD is not clear. This study aimed to investigate the TFs involved in the immune response of NAFLD and provide novel targets for drug development.
Methods:
Microarray data were obtained from liver samples from 26 normal volunteers and 109 NAFLD patients using the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by limma package. Differentially expressed transcription factors (DETFs) were obtained on DEGs combined with Cistrome Cancer database. Immune signatures and pathways hallmark were identified by ssGSSEA and GSVA. The co-regulation network was constructed by the above results. Further, quantitative Real-time Polymerase Chain Reaction (qRT-PCR), Western blot (WB) and Immunohistochemistry (IHC) were used to validate the relationship between GTF2I and NAFLD. CIBERSORT analysis was performed to identify cell types to explore the relationship between differential expression of GTF2I and immune cell surface markers.
Results:
A total of 617 DEGs and six DETFs (ESR1, CHD2, GTF2I, EGR1, HCFC1, SP2) were obtained by differential analysis. Immune signatures and pathway hallmarks were identified by ssGSSEA and GSVA. GTF2I and CHD2 were screened through the co-regulatory networks of DEGs, DETFs, immune signatures and pathway hallmarks. Furthermore, qRT-PCR, WB and IHC indicated that GTF2I but not CHD2 was significantly upregulated in NAFLD. Finally, in silico, our data confirmed that GTF2I has a wide impact on the immune profile by negatively regulating the expression of the chemokine receptor family (227/261, count of significance).
Conclusion:
GTF2I plays a role in NAFLD by negatively regulating the chemokine receptor family, which affects the immune profile. This study may provide a potential target for the diagnosis or therapy of NAFLD.
Insights
Nonalcoholic fatty liver disease (NAFLD) involves immune responses regulated by transcription factors. This study identified GTF2I as a key factor in NAFLD immunity, offering a potential therapeutic target.
Area of Science:
- Hepatology
- Immunology
- Genomics
Background:
- Nonalcoholic fatty liver disease (NAFLD) is a prevalent global health concern.
- Transcription factors (TFs) are crucial in NAFLD metabolism, but their role in immune response is unclear.
- Identifying TFs regulating NAFLD immunity is vital for developing new therapeutic strategies.
Purpose of the Study:
- To investigate transcription factors involved in the immune response during NAFLD development.
- To identify novel therapeutic targets for NAFLD based on immune-regulating TFs.
- To elucidate the specific role of identified TFs in NAFLD pathogenesis.
Main Methods:
- Analysis of microarray data from NAFLD patients and healthy volunteers.
- Identification of differentially expressed genes (DEGs) and transcription factors (DETFs).
- Validation of target gene expression using qRT-PCR, Western blot, and Immunohistochemistry.
Main Results:
- Six DETFs were identified, including GTF2I and CHD2.
- GTF2I was significantly upregulated in NAFLD liver samples.
- GTF2I negatively regulates the chemokine receptor family, impacting the immune profile.
Conclusions:
- GTF2I plays a significant role in NAFLD by modulating the immune profile via the chemokine receptor family.
- GTF2I represents a potential diagnostic or therapeutic target for nonalcoholic fatty liver disease.
- Further research into GTF2I's mechanisms could lead to effective NAFLD treatments.
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