BMPS and Liver: More Questions than Answers

Blanca      Herrera; Aranzazu      Sanchez; Isabel      Fabregat

Abstract

Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily and were first discovered as potent bone homeostasis regulators for their ability to induce endochondral bone formation, ectopic bone formation and fracture repair. A preeminent role of BMP signaling in developmental control of cell type specification, differentiation and organogenesis is also well established. More recently, a role for BMPs in adult tissue homeostasis has started being revealed. Thus, new studies show that BMPs regulate many cellular processes such as proliferation, apoptosis, differentiation and migration in many tissues and organs. As a consequence, dysregulation of BMP activity can have pathological consequences, and there is mounting evidence for the involvement of BMPs in different human diseases. In this review, we have focused on summarizing the present knowledge on the relevance of BMPs in liver physiology and pathophysiology, from the well-recognized role in liver development to the emerging contribution to the function and dysfunction of the adult liver. While no doubts seem to rise about the regulatory activities of BMPs on metabolic pathways in the liver, potential pro- and anti-fibrogenic and tumorigenic actions will likely be a matter of debate during coming years. Collectively, the work here presented provides the basis to consider BMPs as potential targets of intervention in liver diseases.

Keywords: BMP, liver, signaling, fibrosis, hepatocellular carcinoma, development, iron homeostasis, TGF-β, bone homeostasis, tumorigenic actions.