Biology of activin & follistatin

Lab head: Associate Professor David Phillips

The protein activin was originally thought to only play a role as a reproductive hormone responsible for stimulating the production of sperm in men and the production of ovarian follicles, or eggs, in women.

Scientists working in the Centre for Reproduction and Development (CRD) have since discovered that activin also plays a role in modulating liver fibrosis and systemic inflammation. Using a rat model of fibrosis, or scarring, they have shown that activin is part of a critical switch where hepatic stellate cells (liver cells) become activated, proliferate and produce collagen and other fibrotic precursors. Use of follistatin, the high affinity binding protein for activin, reduces the development of liver fibrosis in this model.

In exploring the role activin plays in inflammatory diseases, the scientists have used animal models where diseases like septicemia can be modelled using lipopolysaccharide, the cell wall component of bacteria, to which the body’s immune system is highly sensitive. Using challenge with lipopolysaccharide has shown that activin is one of the earliest blood factors released into the circulation. Of major interest is that the levels of activin in blood may predict the outcome of this response – whether there will be recovery or a bad outcome. They also showed that administration of follistatin to block the activin effects was beneficial and reduced mortality. This was published in the prestigious international journal, Proceedings of the National Academy of Sciences, USA. The information generated in these animal models will allow further examination of the use of activin and follistatin in patients with acute inflammatory syndromes such as septicemia and meningitis, as both diagnostic tests and as therapeutic treatment strategies.