Molecular Mechanism of the Regulatory Effect of Schisandrol A on the Immune Function of Mice Based on a Transcription Factor Regulatory Network

Front Pharmacol. 2021 Dec 20:12:785353. doi: 10.3389/fphar.2021.785353. eCollection 2021.

Abstract

The molecular mechanism of the regulatory effed of schizandrol A (SA) on the immune function of cyclophosphamide-induced immunosuppressive mice was explored in this study. On the basis of 1619 differentially expressed genes related to the regulatory effect of SA on the immune function of mice screened in our previous study, transcription factors and their corresponding target genes were screened in the Transcriptional Regulatory Element Database (TRED), and a transcription factor target gene regulatory network was constructed. The key nodes of the network were statistically analyzed to clarify the role of transcription factors in the regulatory network. The correlation of network genes with diseases was analyzed with an online annotation tool through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, the key factors related to the regulatory effect of SA on the immune function of mice were screened and verified by animal experiments and the detection of related protein expression by western blot analysis. The results showed that SA could alleviate the immunosuppression induced by cyclophosphamide in mice and regulate the protein expression of Jun, Trp53, and Creb1 in the spleen tissue of mice, together with the transcription factors Atf4 and E2f2. SA may thus play a role in the alleviation of some immunity-related diseases (such as cancer) by regulating the immune function of mice through multiple genes and their transcription factors.

Keywords: immune function; microarray; network regulation; schizandrol A; transcription factor.