The Pigment Epithelium-Derived Factor (also known as PEDF and Serpin F1) can be defined as a multifunctional secreted protein. A protein which is only found in vertebrates, it has neurotrophic, anti-tumorigenic and anti-angiogenic functions that make it one of the most studied proteins in the world. A 50 kDa protein (418 amino acids long) that is encoded by the Serpin F1 gene, it has been intrinsically linked to treatments of a variety of conditions such as different forms of cancer and heart disease. Discovered by two scientists – Lincoln Johnson and Joyce Tombran-Tink in the 1980s, it has also been commonly used in treatments of the eye internationally.
It was initially discovered when they were studying retinal cell development within a human. They did this by identifying what the secreted factors were, that were produced by the retinal pigmented epithelium (also known as the RPF). Once realising that the protein was uncharacterised, they coined the term and began exploring what its functions were.
As mentioned above, PEDF has neurotrophic, anti-angiogenic and anti-tumorigenic functions which make it an essential protein within the body. It also suppresses both endothelial cell proliferation (through the p38 MAPK pathway) and retinal neovascularization. In terms of conditions such as cancer, it directly increases apoptosis via the FASL/FAS pathway and acts at inhibiting the proliferation of cancer cells. These, of course, are still being studied and there are no definitive results (as mentioned in the mechanism paragraph below).
Pigment Epithelium-Derived Factor Interactions
There have been three different types of interactions noted between the Pigment Epithelium-Derived Factor and the following molecules – collagen, neuronal cell receptors and glycosaminoglycans of extracellular matrixes. Directly linking with PEDF’s structure, the extracellular matrixes play a key role in surface localization of the activities that exist within PEDF.
The Crystal Structure of the protein was generated successfully when a 2001 one study was carried out. It was discovered that one side of the protein was heavily acidic, whilst the other is basic (which was a heparin binding). The structure itself has 10 alpha helices and 3 beta sheets.
PEDF activities are often thought to be one of the most complex proteins within the body. Because of this, there are a variety of studies that have been taken (such as a study of the correlation between insulin resistance and PEDF) but there have been no definitive results. Although there are claims that it can be used as a biomarker for conditions such as Multiple Sclerosis, the exact mechanisms of actions need to be thoroughly addressed. The same goes for angiogenesis and the claims made that it can assist with diseases such as cancer. As time goes on, the multimodal nature of PEDF will continue to be studied. Enhancing the structure and understanding the chemistry and application of PEDF in biomedicine is essential in order to fully utilise the protein in the treatment of critical conditions including tumours.