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

ABSTRACT: The transforming growth factor-beta (TGF-?) 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-?1 (LAP-TGF-?1). We investigated the role of NRP-1 on Smad signaling in stromal fibroblasts upon TGF-? 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 ?-smooth muscle actin (?-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-?1 that are mediated by distinct Smad proteins and promotes myofibroblast phenotype.

SUBMITTER: Cao Y 

PROVIDER: S-EPMC2951255 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature