Neuropilin-1 mediates divergent R-smad signaling and the myofibroblast phenotype

Ying Cao, Annamaria Szabolcs, Shamit K. Dutta, Usman Yaqoob, Kumaravelu Jagavelu, Ling Wang, Edward B Leof, Raul A. Urrutia, Vijay Shah, Debabrata Mukhopadhyay

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55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)31840-31848
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number41
DOIs
StatePublished - Oct 8 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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