TGF-β Signaling and Organ Fibrosis

About this Webinar:

Transforming growth factor beta1 (TGF-β1) is a powerful fibrogenic cytokine that has been demonstrated to mediate the fibrotic response in various models of progressive fibrosis. TGF-β1 signals through a heteromeric receptor complex comprising a type II ligand-binding receptor and a type I activin-like kinase (ALK) to trigger phosphorylation of downstream effectors known as Smads (canonical pathway) or mitogen-activated protein kinases (noncanonical pathway). TGF-β is a cytokine implicated in tissue repair. During tissue damage, TGF-β is released by parenchymal cells, as well as immune cells such as lymphocytes, macrophages, and platelets, and serves a beneficial role in wound healing by promoting matrix protein synthesis and decreasing matrix protein degradation. It is also believed to increase local collagen and fibronectin levels, which are involved in tissue repair. However, excessive levels of TGF-β can contribute to the pathogenesis of tissue fibrosis and is especially observed in fibrosis of organs such as the lung, heart, kidney, and liver following a physical injury. In fibrotic tissues, TGF-β signaling pathways are constantly activated despite the condition of the original injury. Additionally, TGF-β has been shown to activate fibroblasts, one of the key mediators in fibrotic responses. While fibroblasts are typically associated with tissue repair through the production of extracellular matrix (ECM), which is used to regenerate tissue structure, consistent stimulation by TGF-β can result in fibroblasts differentiating into myofibroblasts, which have an increased rate of matrix production, promoting fibrosis.