Wnt Pathway

Abstract

The Wnt pathway plays a critical role in the development of multicellular organisms.1,2 It shows evolutionary conservation across a wide range of species, ranging from the freshwater polyp Hydra to worms, flies, and vertebrates. Since the 1980s our knowledge of Wnt signal transduction has expanded tremendously. This family of proteins comprises a group of 19 secreted lipid-modified glycoproteins that not only play a crucial role in the regulation of embryogenesis and development but also cell proliferation, differentiation, polarity, migration, and invasion.1,2 Abnormal Wnt signaling has been associated with many human diseases, ranging from cancer to degenerative diseases. Thus studies of Wnt signaling have opened up new avenues in biomedical research, including molecular embryology, stem cell biology, tumorigenesis, regenerative medicine, and rational drug discovery.3 Interestingly, in this issue of Arteriosclerosis Thrombosis and Vascular Biology , Pereira and colleagues highlight the involvement of the Wnt pathway in the sustained inflammation in sepsis. This study contributes to the accumulating evidence that the Wnt pathway also plays a distinct role in inflammation and immunity. See accompanying article on page 504 Pereira and colleagues suggest that Wnt5a is a highly specific autocrine and paracrine macrophage-derived effector molecule which triggers inflammation. Altered macrophage functions contribute to the pathogenesis of many infectious, immunologic, and inflammatory disease processes in addition to sepsis, such as rheumatoid arthritis and atherosclerosis. Development of novel pharmacological modulators of macrophage activity represents an important strategy for the prevention and treatment of these inflammation-related diseases. Consequently the findings of Pereira and colleagues may have wider impact by relevance …