Abstract
Uterine fibroids represent the most common benign tumors of the uterus. They are considered a typical fibrotic disorder. In fact, the extracellular matrix (ECM) proteins—above all, collagen 1A1, fibronectin and versican—are upregulated in this pathology. The uterine fibroids etiology has not yet been clarified, and this represents an important matter about their resolution. A model has been proposed according to which the formation of an altered ECM could be the result of an excessive wound healing, in turn driven by a dysregulated inflammation process. A lot of molecules act in the complex inflammatory response. Macrophages have a great flexibility since they can assume different phenotypes leading to the tissue repair process. The dysregulation of macrophage proliferation, accumulation and infiltration could lead to an uncontrolled tissue repair and to the consequent pathological fibrosis. In addition, molecules such as monocyte chemoattractant protein-1 (MCP-1), granulocyte macrophage-colony-stimulating factor (GM-CSF), transforming growth factor-beta (TGF-β), activin A and tumor necrosis factor-alfa (TNF-α) were demonstrated to play an important role in the macrophage action within the uncontrolled tissue repair that contributes to the pathological fibrosis that represents a typical feature of the uterine fibroids.
Highlights
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The myometrium is composed of three smooth muscle layers: the subvascular layer, which is quite thin; the vascular layer, which is rather strong and well-perfused; and the supravascular layer, which is composed of a complex of crossing muscle fibers
A few years ago, we demonstrated that ulipristal acetate (UPA) can exert a downregulation effect at the level of the mRNA of activin A, a pro-fibrotic factor for leiomyoma
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The ECM was suggested to represent a reservoir for growth factors, cytokines, chemokines, angiogenic and inflammatory response mediators, and proteases [43,50,51,52,53], which are all molecules thought to be involved in the initiation and development of the uterine fibroids [11].
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