Figure 3.

Illustration of the macrophages’ (yellow in the figure) role in uterine fibroids. Monocyte chemoattractant protein-1 (MCP-1) takes part in the regulation of the macrophages’ infiltration. The granulocyte macrophage-colony-stimulating factor (GM-CSF) is considered the most important growth factor for macrophage proliferation. GM-CSF can establish regulatory interactions with the transforming growth factor-beta (TGF-β), which was shown to be the most important growth factor secreted by macrophages. In uterine fibroids, TGF-β is overexpressed and it contributes to myofibroblast differentiation. Macrophages also secrete activin A, an immuno-regulator belonging to the TGF-β family. Activin A develops a pro-fibrotic action leading to the expression of the extracellular matrix (ECM) proteins (represented by the blue net in the figure), which are overexpressed in uterine fibroids. Activin A mRNA expression in uterine fibroids is upregulated by the tumor necrosis factor-alfa (TNF-α), an inflammatory mediator mainly produced by macrophages. On the right, above the image that portrays the myofibroblasts, the uterine fibroids (red in the figure) with the myometrium (pink in the figure), the endometrium (brown in the figure), the macrophages (yellow in the figure) and the overexpressed ECM proteins (blue net in the figure) are represented. The blood vessels within endometrium are also represented (red lines in the figure).