Activin E is a protein molecule with diverse roles within the body. It functions as a signaling molecule, transmitting messages between cells to regulate various biological processes.
Understanding Activin E’s Identity
Activin E is a member of the transforming growth factor-beta (TGF-β) superfamily of proteins, a large group known for regulating cell growth and differentiation. This protein exists as a homodimer, formed by two identical protein subunits linked together. Its structure allows it to interact with other molecules to carry out its functions.
The INHBE gene, which provides instructions for making Activin E, was identified in mouse liver tissue, showing primary expression in the liver. Activin E signals predominantly through activin receptor-like kinase 7 (ALK7), a type I receptor. It also binds to activin type II receptors, activin receptor type IIA (ActRIIA) and activin receptor type IIB (ActRIIB). Once bound, Activin E initiates an intracellular signaling cascade, primarily activating the SMAD2/3 pathway, which influences gene expression within the cell.
Activin E’s Roles in the Body
Activin E plays a role in regulating the body’s energy balance by influencing fat storage in adipose tissue. It achieves this by suppressing lipolysis, the breakdown of fats. This suppression promotes fat accumulation and contributes to the enlargement of fat cells, known as adipocyte hypertrophy.
Activin E also impacts metabolic genes, influencing how the body manages its energy. Its presence can lead to reduced lipid mobilization, meaning less fat is released from storage for energy use. The broader activin family, to which Activin E belongs, is involved in biological processes such as cell growth, differentiation, and tissue repair.
Activins contribute to regeneration by stimulating cell division and the formation of new cells, particularly in contexts like wound healing. For instance, activin is strongly expressed in wounded skin, and increased levels can enhance scar formation and improve healing. In the reproductive system, activins are involved in the development of ovarian follicles, ovulation, and the formation of the corpus luteum in females. They also modulate hormone secretion in the ovaries and regulate spermatogenesis and testosterone production in males.
Beyond these functions, activins influence the morphogenesis, or structural development, of various branching organs, including the prostate, lungs, and kidneys. Some activin family members, like Activin B, are involved in central nervous system development, promoting the proliferation and maturation of oligodendrocytes, cells that form myelin. Another family member, Activin A, can increase the expression of type-I collagen, suggesting an influence on fibroblast activity.
Activin E and Health Conditions
Dysregulation of Activin E levels can be observed in various health conditions, particularly those involving metabolic imbalances. Elevated Activin E can contribute to adipose dysfunction, characterized by impaired fat tissue function, and may lead to inflammation within these tissues. Conversely, a reduction in Activin E in mice can enhance adipose lipolysis, resulting in lower fat mass. These findings link Activin E to the regulation of overall adiposity.
The broader activin system, including Activin E, has implications in inflammatory and fibrotic diseases. Inhibiting activin’s actions can reduce inflammation, tissue damage, and fibrosis in various disease models. For example, Activin A and Activin B levels are elevated in the alveolar and inflammatory cells of patients with idiopathic pulmonary fibrosis, a chronic lung disease. An antagonist to Activin A has been shown to reduce bleomycin-induced pulmonary fibrosis, highlighting a potential therapeutic target.
The dysregulation of the entire activin-follistatin-inhibin system has been associated with reproductive and pregnancy disorders, including polycystic ovary syndrome, ectopic pregnancy, miscarriage, and gestational diabetes. Activin A and Activin B have also been observed to contribute to the progression of certain tumors, particularly those affecting reproductive organs.