Transglutaminases in fibrosis - overview and recent advances

Transglutaminases (TG) are a family of protein crosslinking enzymes that are capable of stiffening and insolubilizing proteins and creating protein networks, and thereby altering biological functions of proteins. Their role in fibrosis progression has been widely investigated with focus on kidney, lung, liver, and heart where activity is triggered by various stimuli including hypoxia, inflammation, and hyperglycemia. TG2 has been considered one of the key enzymes in the pathogenesis of fibrosis mainly through TGF-b signaling and matrix crosslinking mechanisms. Although TG2 has been most widely studied in this context, the involvement of other TGs; TG1, and Factor XIII-A is beginning to emerge. This minireview highlights the major steps taken in the TG and fibrosis research and summarizes most recent advances and contributions of TG2, TG1 and FXIII-A to progression of fibrosis in various animal models. Also, their mechanisms of action as well as therapeutic prospects are discussed.