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Neuropilin-1 mediates divergent R-Smad signaling and the myofibroblast phenotype. J Biol Chem 2010 Oct 08;285(41):31840-8 PMID: 20675371 PMCID: PMC2951255

Pubmed ID

20675371

DOI

10.1074/jbc.M110.151696

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.

Author List

Cao Y, Szabolcs A, Dutta SK, Yaqoob U, Jagavelu K, Wang L, Leof EB, Urrutia RA, Shah VH, Mukhopadhyay D

Authors

Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
Ling Wang MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




Scopus

2-s2.0-77957787219   48 Citations

MESH terms used to index this publication - Major topics in bold

Actins
Animals
Cell Line, Transformed
Fibroblasts
Gene Expression Regulation
Hepatic Stellate Cells
Humans
Liver
Mice
Mice, Knockout
Myoblasts
Neuropilin-1
Phosphorylation
Signal Transduction
Smad Proteins, Receptor-Regulated
Transforming Growth Factor beta1
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad