Activin A is a protein that serves as a signaling molecule, facilitating cell communication throughout the body. It is a member of the transforming growth factor-beta (TGF-β) superfamily.
What is Activin A and Where is it Found?
Activin A is structured as a dimeric protein, formed from two protein subunits. It is synthesized as a larger precursor that undergoes processing to become biologically active. This protein is widely distributed throughout the body.
It is found in locations such as the gonads (ovaries and testes), brain, pituitary gland, bone marrow, skin, lungs, liver, and gut. This broad distribution indicates its role as a messenger molecule facilitating communication among various cell types. Its functions are similar in humans and animals, as its amino acid sequence is highly conserved across species.
Its Diverse Roles in Development and Body Function
Activin A contributes to various physiological processes, including reproduction, embryonic development, and the maintenance of tissue health.
In the reproductive system, activin A is involved in gonadal function, including ovarian follicle development and sperm production (spermatogenesis). It also helps regulate hormone secretion, notably by influencing the release of follicle-stimulating hormone (FSH) from the pituitary gland. Activin A can increase the number of FSH receptors in ovarian cells to promote follicle growth.
During early embryonic development, activin A contributes to the initial patterning of the embryo and the differentiation of cells into various tissues and organs. It induces the formation of mesodermal and endodermal tissues. Activin A influences the embryonic body plan by affecting mesoderm induction.
Activin A also participates in tissue homeostasis and repair. It plays a role in wound healing by stimulating cells involved in repair. It is involved in hematopoiesis (blood cell formation), particularly by enhancing erythropoiesis (red blood cell production). Activin A is also linked to inflammation and metabolism, contributing to the body’s overall balance and defense mechanisms.
Activin A’s Link to Health and Disease
Dysregulation of activin A levels or activity can contribute to a range of health conditions, highlighting its involvement in both normal bodily functions and disease states. Both an excess or deficiency of activin A can lead to adverse effects.
Infertility in both males and females has been linked to imbalances in activin A. Activin A is a major regulator of testicular and ovarian development, and its dysregulation is associated with reproductive pathologies. Mutations in activin A are also connected to reproductive cancers.
Activin A’s role in cancer is complex, acting differently depending on the cancer type. It can sometimes promote tumor growth and spread, as seen in certain ovarian or prostate cancers, while in other instances, it may act to suppress tumor development. For example, it can induce apoptosis and inhibit proliferation in some cancer cell lines, but enhance proliferation in others like lung fibroblasts and certain lung cancer cells.
The protein is also implicated in inflammatory and fibrotic diseases. Activin A levels can increase in both acute and chronic inflammation, correlating with disease severity. It promotes inflammation by stimulating the production of inflammatory mediators such as TNF-α, IL-6, and IL-1β. This involvement extends to the development of fibrosis, which is the excessive formation of fibrous connective tissue, in organs like the kidneys, lungs, and liver. Emerging research also suggests links between activin A and metabolic conditions such as obesity and diabetes.
Future Directions: Activin A as a Therapeutic Target
Research into activin A’s functions has opened avenues for its potential as a therapeutic target in various diseases. Scientists are actively exploring methods to modulate its activity to develop new medical treatments.
One approach involves using inhibitors or activators to control activin A’s effects in the body. For instance, an investigational antibody called garetosmab, which blocks activin A, is being studied for the treatment of fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder characterized by abnormal bone formation. In a phase 2 trial, garetosmab was shown to inhibit new heterotopic bone lesion formation in FOP patients.
Targeting activin A is also being investigated for fibrotic disorders, certain cancers, and reproductive issues. By influencing activin A signaling, researchers hope to limit tumor growth and spread, improve drug responses, enhance anti-tumor immune responses, and alleviate conditions like cancer-associated cachexia, bone loss, and anemia. This area of research is active and holds promise for future medicine, though therapeutic possibilities are still in development.