Liver fibrosis refers to a pathological condition in which there is excessive deposition of scar tissue in the liver as a result of chronic inflammation within the liver tissue. Viral infections, excess alcohol consumption, obesity cause long-term liver damage, and the wound healing response to this damage occurs. The progression of Liver fibrosis is mainly caused by the accumulation of extracellular matrix (ECM) proteins, especially excessive accumulation of collagen. Excessive accumulation of ECM activates hepatic stellate cells (HSC), and HSC play an important role in the progression of fibrosis by inducing collagen deposition. Currently, liver transplantation is the only treatment for advanced stages of liver diseases including fibrosis, cirrhosis, and cancer. In the case of fibrosis, as understanding of fibrogenesis has improved, several drug candidates are being tested, but none have been approved.

Translationally controlled tumor protein (TCTP) is known as histamine-releasing factor and is present in all eukaryotes. It is a highly conserved protein involved in cell cycle, proliferation, and survival that is essential for eukaryotic cells. TCTP exists as dimeric or monomeric TCTP, and dimeric TCTP is known to have better cytokine-like activity than monomeric TCTP. Extracellular TCTP undergoes dimerization and induces secretion of inflammatory cytokines. It is known that immune disorders and allergies are caused by TCTP dysregulation. Additionally, TCTP is an emerging tumor therapeutic target because it is overexpressed in a variety of malignancies. Recently, studies have linked TCTP to liver proliferation and regeneration. Therefore, we aimed to study the association between TCTP and liver fibrosis.

Dimeric TCTP (dTCTP) was increased in a mouse model with induced liver fibrosis. Additionally, dTCTP promotes fibrosis by activating hepatic stellate cells. Dimeric TCTP-binding peptide 2 (dTBP2), a dTCTP inhibitor, treatment reduced inflammatory cytokines and fibrosis markers. Cumulated results suggest that inhibiting dTCTP through dTBP2 alleviates liver fibrosis. Therefore, dTCTP is an effective target in the progression of liver fibrosis, and the treatment of dTBP2 could be a potential therapeutic agent to treat liver fibrosis.