Abstract
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.
Keywords
activin A - uterine fibroid - inflammation - fibrosis
