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 H. Shah, Debabrata Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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
Issue number41
StatePublished - Oct 8 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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