Activin A in Inflammation, Tissue Repair, and Fibrosis: Possible Role as Inflammatory and Fibrotic Mediator of Uterine Fibroid Development and Growth
The growth factor activin A belongs to the transforming growth factor-β superfamily and was initially isolated as an inducer of follicle-stimulating hormone secretion. Activin A was later found to play roles in cell proliferation, differentiation, apoptosis, and metabolism. More recently, activin A has also been recognized as a novel player in mediating inflammation, immunity, wound repair, and fibrosis. Elevated levels of activin A during inflammation are responsible for the increased production of extracellular matrix in different pathological conditions, including fibroids. Our group has demonstrated a profibrotic role of activin A in leiomyoma growth. Uterine leiomyoma can be considered as a fibrotic disorder that initiates from myometrial smooth muscle layer of uterus in reproductive-age women and that is driven by a strong inflammatory component. In fertile women, transient inflammation is a physiological and essential process during menstruation, ovulation, and parturition. However, tissue injury from extravasated menstrual blood and/or an altered response to harmful stimuli, such as pathogens, damaged cells, or irritants, can establish chronic inflammation in the uterus, ultimately leading to dysregulated tissue repair. Myofibroblasts are key cells in normal repair and the chronic tissue remodeling characteristic for fibrosis and uterine leiomyoma. In this review, we discuss the role of activin A in inflammation, tissue repair, and fibrosis and we elaborate the hypothesis that it plays a central role in myofibroblast activation and leiomyoma development and growth.