Regulation of Macrophage Polarization by miR-449a/Cripto-1-PI3K/AKT/NF- κ B Signaling Pathway in Allogeneic Transfusion Mice

Biomed Res Int. 2023 Jan 6:2023:1277258. doi: 10.1155/2023/1277258. eCollection 2023.

Abstract

In this study, the expression of Cripto-1 and the role of macrophage polarization in immune response after allogeneic transfusion were analyzed by constructing a mouse model of allogeneic transfusion. In order to analyze the effects of miR-449a on the PI3K/AKT/NF-κB signaling pathway and the expression of downstream related regulatory factors under normal and abnormal conditions, we adopt in vitro and in vivo experiments separately. The molecular mechanism of PI3K/AKT/NF-κB signaling pathway was analyzed by blocking or activating gene expression and western blotting. Experiment in vitro has confirmed that inhibition of miR-449a increased the protein expression of Cripto-1. In vivo experiments confirmed that allogeneic transfusion reduced the expression of Cripto-1, which further inhibited NF-κB signaling pathway through AKT/PI3K phosphorylation, regulated macrophage polarization, inhibited M1 polarization of macrophages, promoted M2 polarization, and thus affected immune response of the body.

MeSH terms

  • Animals
  • Hematopoietic Stem Cell Transplantation*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Macrophages / metabolism
  • Mice
  • MicroRNAs* / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs