The Next Battlefield Where Transforming Growth Factor-β and Endoglin Draw Their Double-Edged Swords?
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Regenerative tissue repair after injury is a delicate balance between pivotal biological processes, such as cell growth and differentiation, angiogenesis, and extracellular matrix remodeling. The notice that damage repair comes with enhanced angiogenic and profibrotic responses has inspired the scientific community with the idea that molecules involved in collagen turnover and proteolysis may act as biomarkers to predict remission or activation of chronic inflammatory diseases in which fibrosis is one of the major underlying key players.
See accompanying article on page 49
Transforming growth factor-β (TGF-β) is a critical growth factor in tissue repair. TGF-β belongs to a large family of growth factors to which also the bone morphogenetic proteins (BMPs) belong.1 TGF-β has many functions such as inhibition of epithelial and endothelial cell growth, stimulation of mesenchymal cell growth, and diminishing the inflammatory response, but its most important role in tissue repair is to promote extracellular matrix turnover.
Although TGF-β1 has proarteriogenic and angiogenic effects, depending on the context and concentration, TGF-β can also be antiangiogenic, inhibiting the growth of endothelial cells.2 Therefore, it plays a pivotal role during vascular homeostasis and maintenance. TGF-β1 seems a double-edged sword in vascular occlusive diseases. On one hand, it enhances smooth muscle cell proliferation and stimulates extracellular matrix production, 2 key components of restenosis and vessel remodeling. On the other hand, an increase in smooth muscle cell content and a thick fibrotic cap are also features of stable atherosclerotic lesions that are less prone to rupture.
Endoglin is an accessory TGF-β receptor and a modulator of TGF-β signaling.3 Endoglin plays an important regulatory role in balancing the proangiogenic and antiangiogenic and fibrotic response of TGF-β. Endoglin exerts its function by interacting with the TGF-β type II receptor and the type 1 receptors ALK1 (activin receptor-like kinase) and ALK5 and …