Knockdown of D-dopachrome Tautomerase Inhibits Cell Proliferation in Human HepG2 Cell Line
Asuka Takahashi1, Takeo Iwata2, Kikuji Yamashita1
1Department of Functional Morphology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Background/Aim:
D-dopachrome tautomerase (DDT) is a macrophage migration inhibitory factor (MIF) homolog that promotes cell growth via CD74, a MIF cell surface receptor, in some types of tumors. We previously found that DDT acts as an anti-obesity adipokine independent of MIF. To understand the intrinsic properties of these two cytokines, a comparison of their actions in various tissues is necessary. In this study, we investigated the involvement of DDT in HepG2 cell (a human hepatoma cell line) proliferation, which is known to be promoted by MIF.
Materials And Methods:
Cell proliferation and gene expression were evaluated in HepG2 cells expressing short hairpin RNA against the DDT gene.
Results:
Inhibition of cell proliferation and reduced expression levels of cyclin D1 were observed in DDT-knockdown HepG2 cells. The inhibited proliferation was restored by administration of recombinant DDT.
Conclusion:
DDT promotes cell proliferation in HepG2 cells; therefore, its action may be similar to that of MIF.
Insights
D-dopachrome tautomerase (DDT) promotes HepG2 cell proliferation, similar to macrophage migration inhibitory factor (MIF). Inhibiting DDT reduced cell growth, which was restored by adding recombinant DDT.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- D-dopachrome tautomerase (DDT) is a macrophage migration inhibitory factor (MIF) homolog.
- DDT promotes tumor cell growth via CD74 and acts as an anti-obesity adipokine.
- MIF is known to promote HepG2 cell proliferation.
Purpose of the Study:
- To investigate the role of DDT in HepG2 cell proliferation.
- To compare the intrinsic properties of DDT and MIF.
Main Methods:
- HepG2 cells were engineered to express short hairpin RNA targeting the DDT gene.
- Cell proliferation assays were performed.
- Gene expression levels, specifically for cyclin D1, were analyzed.
Main Results:
- Knockdown of DDT inhibited HepG2 cell proliferation.
- Reduced expression of cyclin D1 was observed in DDT-knockdown cells.
- Recombinant DDT administration restored the inhibited cell proliferation.
Conclusions:
- DDT promotes cell proliferation in HepG2 cells.
- The action of DDT in HepG2 cells may be similar to that of MIF.
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