Study on the regulation of Cordyceps militaris polypeptide on the immune function of mice based on transcription factor regulatory network

Background: The pathogenesis of the abnormality of immune system is still not clear at present. Chemosynthetic drugs, human or animal immune products and microbiological drugs are used as the main drugs in clinic currently, but these drugs have different side effects. So the researchers turned to the safer natural products in order to find the immunomodulatory active substances from the natural products and their extracts. Methods: Immunosuppressive mice were induced by cyclophosphamide and administered with Cordyceps miliaris polypeptide (CMP) for the study on the effect of CMP on the immune function of mice and its mechanism. Based on the 1748 differential gene sets selected in our previous work, the transcription factors and their corresponding target genes were screened by integrating TRED (Transcriptional Regulatory Element Database), the transcriptional factor-target gene regulatory network was constructed, then the role of transcription factors in the regulatory network was elucidated by statistically analyzing the key nodes, and finally, the correlation of network genes with diseases was analyzed by using DAVID database. Results: The results of animal experiments showed that CMP could increase the immune organ indexes, the number of white blood cells, the degree of delayed allergy and the content of hemolysin in the serum of mice. CMP was found to be involved in the regulation of immune function in mice through gene Kdr, Spp1, Ptgs2, Rel, Smad3, and transcription factor Ets1, E2f2 and E2f1, in which E2f family played an important role, and its main regulatory pathways were PI3K-Akt signaling pathway and TNF signaling pathway. Conclusion: CMP can improve the immunity of mice. CMP can regulate the immune function of mice by multiple genes and transcription factors, and may also play a role in immune-related diseases (cancer).