Neuropilin-1 mediates divergent R-Smad signaling and the myofibroblast phenotype.

Publication Type:

Journal Article

Source:

The Journal of biological chemistry, Volume 285, Issue 41, p.31840-8 (2010)

Keywords:

Actinsdigestive disease, digestive deseases Animalsdigestive disease, digestive deseases Cell Line, Transformeddigestive disease, digestive deseases Fibroblastsdigestive disease, digestive deseases Gene Expression Regulationdigestive disease, digestive deseases Hepatic Stellate Cellsdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Liverdigestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, Knockoutdigestive disease, digestive deseases Myoblastsdigestive disease, digestive deseases Neuropilin-1digestive disease, digestive deseases Phosphorylationdigestive disease, digestive deseases Signal Transductiondigestive disease, digestive deseases Smad Proteins, Receptor-Regulateddigestive disease, digestive deseases Transforming Growth Factor beta1

Abstract:

The transforming growth factor-beta (TGF-β) superfamily is one of the most diversified cell signaling pathways and regulates many physiological and pathological processes. Recently, neuropilin-1 (NRP-1) was reported to bind and activate the latent form of TGF-β1 (LAP-TGF-β1). We investigated the role of NRP-1 on Smad signaling in stromal fibroblasts upon TGF-β stimulation. Elimination of NRP-1 in stromal fibroblast cell lines increases Smad1/5 phosphorylation and downstream responses as evidenced by up-regulation of inhibitor of differentiation (Id-1). Conversely, NRP-1 loss decreases Smad2/3 phosphorylation and its responses as shown by down-regulation of α-smooth muscle actin (α-SMA) and also cells exhibit more quiescent phenotypes and growth arrest. Moreover, we also observed that NRP-1 expression is increased during the culture activation of hepatic stellate cells (HSCs), a liver resident fibroblast. Taken together, our data suggest that NRP-1 functions as a key determinant of the diverse responses downstream of TGF-β1 that are mediated by distinct Smad proteins and promotes myofibroblast phenotype.