Roles and mechanisms of action of HNF‑4α in the hepatic differentiation of WB‑F344 cells

  • Authors:
    • Yumeng Shi
    • Dehua Zhou
    • Bingyi Wang
    • Deren Zhou
    • Baomin Shi
  • View Affiliations

  • Published online on: December 3, 2018     https://doi.org/10.3892/ijmm.2018.4010
  • Pages: 1021-1032
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Abstract

Hepatocyte nuclear factor 4 α (HNF‑4α) is a nuclear receptor and mediates hepatic genes. WB‑F344 liver epithelial cells can differentiate into hepatocytes. The present study aimed to examine the roles and mechanisms of action of HNF‑4α on the hepatic differentiation of WB‑F344 cells. WB‑F344 cells were divided into a normal cell group (WB‑F344), empty vector group (PLKO), and gene silencing group (PLKO‑SH). The expression levels of HNF‑4α were measured using reverse transcription‑quantitative polymerase chain reaction analysis. Proliferation of the cells was determined using a Cell Counting kit‑8 assay. Based on western blot analysis, the protein levels of α‑fetoprotein (AFP), albumin (ALB) and cytokeratin 19 (CK19) were determined. The positive cell rates of the three groups were assessed using periodic acid‑Schiff (PAS) staining. Following construction of an RNA‑sequencing library, differentially expressed genes (DEGs) between the HNF‑4α‑silenced and normal samples were screened using the limma package and enrichment analysis was conducted using the DAVID tool. Protein‑protein interaction (PPI) and microRNA‑targeted regulatory networks were constructed in Cytoscape software. The PLKO‑SH group exhibited a lower mRNA level of HNF‑4α, higher protein level of AFP, lower protein levels of ALB and CK19, increased cell proliferation, and a lower PAS‑positive cell rate. The HNF‑4α‑silenced and normal samples differed in 499 DEGs. In the PPI network, matrix metallopeptidase 9 (MMP9), early growth response 1 (EGR1), SMAD family member 2 (SMAD2), and RAS‑related C3 botulinum substrate 2 (RAC2) were key nodes. HNF‑4α may promote the differentiation of WB‑F344 cells into hepatocytes by targeting MMP9, EGR1, SMAD2 and RAC2.
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February-2019
Volume 43 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Shi Y, Zhou D, Wang B, Zhou D and Shi B: Roles and mechanisms of action of HNF‑4α in the hepatic differentiation of WB‑F344 cells . Int J Mol Med 43: 1021-1032, 2019.
APA
Shi, Y., Zhou, D., Wang, B., Zhou, D., & Shi, B. (2019). Roles and mechanisms of action of HNF‑4α in the hepatic differentiation of WB‑F344 cells . International Journal of Molecular Medicine, 43, 1021-1032. https://doi.org/10.3892/ijmm.2018.4010
MLA
Shi, Y., Zhou, D., Wang, B., Zhou, D., Shi, B."Roles and mechanisms of action of HNF‑4α in the hepatic differentiation of WB‑F344 cells ". International Journal of Molecular Medicine 43.2 (2019): 1021-1032.
Chicago
Shi, Y., Zhou, D., Wang, B., Zhou, D., Shi, B."Roles and mechanisms of action of HNF‑4α in the hepatic differentiation of WB‑F344 cells ". International Journal of Molecular Medicine 43, no. 2 (2019): 1021-1032. https://doi.org/10.3892/ijmm.2018.4010