Tryptase-like proteases: A novel perspective for fibrosis

Fibrosis, as a chronic disease, is affecting people's health. The main pathological characteristic is the deposition of fibrous connective tissue, such as collagen and fibronectin, which are components of the extracellular matrix (ECM). When fibrosis is not treated in time, it can lead to permanent scarring, organ dysfunction, and eventually death. Recent reports indicated that fibrosis may be reversible. Therefore, it is considerable significance to find potential gene targets or biomarkers for anti-fibrosis treatment. Trypsin-like proteases (TLPs), a family of serine enzymes predominantly specific for basic residues such as lysine and arginine in the P1 position, are widely distributed in the body. TLPs play crucial role in various physiological processes, including digestion, blood coagulation, wound healing, and immunity. They could promote the proliferation, differentiation, and activation of fibroblasts, as well as collagen production, either by cleaving and activating PARs receptors or by directly hydrolyzing collagen during fibrotic diseases. This review aims to clarify the connection between TLPs and fibrotic diseases through recent studies. There is an increasing agreement that TLPs play a potential therapeutic target for various fibrotic conditions.