Pleiotropic roles of TGFβ/Smad signaling in the progression of chronic liver disease.

A wide range of pathophysiological changes are involved in the progression of chronic liver disease (CLD). The multifunctional cytokine transforming growth factor β (TGFβ) can cross talk with other signaling pathways and mediate nearly every aspect of cell physiology from growth to differentiation and cell death. TGFβ can maintain immune response homeostasis and mediate wound-healing responses. Additionally, not only can TGFβ prevent the occurrence of hepatocarcinoma by regulating the proliferation of hepatic progenitor cells, TGFβ can also play important roles in blunting inflammation by interfering with tumor inhibition response generated by inflammatory mediators. The TGFβ/Smad signaling pathway is an important response that is mediated by TGFβ. This pathway also plays multiple functions in the progression of chronic liver disease. The pleiotropic effects of TGFβ and TGFβ/Smad signaling create challenges in the treatment of CLD under conditions that might interfere with the TGFβ signaling pathway. Detailed understanding of the pleiotropic roles of TGFβ signaling in CLD might assist in the selection of more accurate therapeutic approaches, and in the targeting of the right type of cell in the development of treatment strategies, and ultimately in achieving the desired therapeutic effects.