MIF and JAB1 enhance TGF-beta signaling in transdifferentiating hepatic stellate cells

Hepatic fibrosis is a wound healing process mainly characterized by accumulation of extracellular matrix in response to liver injury. As a consequence of chronic tissue damage hepatic stellate cells undergo a process of transdifferentiation into myofibroblasts. This process is promoted by TGF-beta, a key mediator of fibrosis. The intracellular effectors of TGF-beta signaling, the Smad2/3 proteins, are activated by receptors and translocate as a complex with Smad4, into the nucleus, where they regulate transcription. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that broadly controls ce…