Roles of transforming growth factor-β signaling in liver disease.

In this editorial we expand the discussion on the article by Zhang published in the recent issue of the . We focus on the diagnostic and therapeutic targets identified on the basis of the current understanding of the molecular mechanisms of liver disease. Transforming growth factor-β (TGF-β) belongs to a structurally related cytokine super family. The family members display different time- and tissue-specific expression patterns associated with autoimmunity, inflammation, fibrosis, and tumorigenesis; and, they participate in the pathogenesis of many diseases. TGF-β and its related signaling pathways have been shown to participate in the progression of liver diseases, such as injury, inflammation, fibrosis, cirrhosis, and cancer. The often studied TGF-β/Smad signaling pathway has been shown to promote or inhibit liver fibrosis under different circumstances. Similarly, the early immature TGF-β molecule functions as a tumor suppressor, inducing apoptosis; but, its interaction with the mitogenic molecule epidermal growth factor alters this effect, activating anti-apoptotic signals that promote liver cancer development. Overall, TGF-β signaling displays contradictory effects in different liver disease stages. Therefore, the use of TGF-β and related signaling pathway molecules for diagnosis and treatment of liver diseases remains a challenge and needs further study. In this editorial, we aim to review the evidence for the use of TGF-β signaling pathway molecules as diagnostic or therapeutic targets for different liver disease stages.