Fibroblast Activation Protein Alpha (FAP) in Fibrosis: Beyond a Perspective Marker for Activated Stromal Cells?

The development of tissue fibrosis is a complex process involving the interaction of multiple cell types, which makes the search for antifibrotic agents rather challenging. So far, myofibroblasts have been considered the key cell type that mediated the development of fibrosis and thus was the main target for therapy. However, current strategies aimed at inhibiting myofibroblast function or eliminating them fail to demonstrate sufficient effectiveness in clinical practice. Therefore, today, there is an unmet need to search for more reliable cellular targets to contribute to fibrosis resolution or the inhibition of its progression. Activated stromal cells, capable of active proliferation and invasive growth into healthy tissue, appear to be such a target population due to their more accessible localization in the tissue and their high susceptibility to various regulatory signals. This subpopulation is marked by fibroblast activation protein alpha (FAP alpha). For a long time, FAP alpha was considered exclusively a marker of cancer-associated fibroblasts. However, accumulating data are emerging on the diverse functions of FAP alpha, which suggests that this protein is not only a marker but also plays an important role in fibrosis development and progression. This review aims to summarize the current data on the expression, regulation, and function of FAP alpha regarding fibrosis development and identify promising advances in the area.