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P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype.

Publication ,  Journal Article
Pan, D; Zhe, X; Jakkaraju, S; Taylor, GA; Schuger, L
Published in: J Clin Invest
November 2002

P311, also called PTZ17, was identified by suppressive subtraction hybridization as potentially involved in smooth muscle (SM) myogenesis. P311 is an 8-kDa protein with several PEST-like motifs found in neurons and muscle. P311 transfection into two fibroblast cell lines, NIH 3T3 and C3H10 T1/2, induced phenotypic changes consistent with myofibroblast transformation, including upregulation of SM alpha-actin and SM22, induction of FGF-2, VEGF, PDGF, and PDGF receptors, upregulation of integrins alpha3 and alpha5, and increased proliferation rate. The P311-mediated changes differed, however, from the well-characterized myofibroblast in that P311 inhibited TGF-beta1, TGF-beta receptor 2, and TGF-beta1-activating MMP-2 and MMP-9, with the resultant decrease in collagen 1 and 3 expression. The effect of P311 on collagen was overcome by exogenous TGF-beta1, indicating that the cells were responsive to TGF-beta1 paracrine stimulus. In support of a role for P311 in vivo, immunohistochemical examination of human wounds showed P311 only in myofibroblasts and their activated precursors. To our knowledge, these studies are the first to implicate P311 in myofibroblast transformation, to demonstrate that transformation may occur independently of TGF-beta1, and to suggest that P311 may prevent fibrosis.

Duke Scholars

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

November 2002

Volume

110

Issue

9

Start / End Page

1349 / 1358

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Tensile Strength
  • Platelet-Derived Growth Factor
  • Phenotype
  • Oncogene Proteins
  • Nerve Tissue Proteins
  • Mice
  • Immunology
  • Humans
 

Citation

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Pan, D., Zhe, X., Jakkaraju, S., Taylor, G. A., & Schuger, L. (2002). P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype. J Clin Invest, 110(9), 1349–1358. https://doi.org/10.1172/JCI15614
Pan, Desi, Xiaoning Zhe, Sandhya Jakkaraju, Gregory A. Taylor, and Lucia Schuger. “P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype.J Clin Invest 110, no. 9 (November 2002): 1349–58. https://doi.org/10.1172/JCI15614.
Pan D, Zhe X, Jakkaraju S, Taylor GA, Schuger L. P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype. J Clin Invest. 2002 Nov;110(9):1349–58.
Pan, Desi, et al. “P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype.J Clin Invest, vol. 110, no. 9, Nov. 2002, pp. 1349–58. Pubmed, doi:10.1172/JCI15614.
Pan D, Zhe X, Jakkaraju S, Taylor GA, Schuger L. P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype. J Clin Invest. 2002 Nov;110(9):1349–1358.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

November 2002

Volume

110

Issue

9

Start / End Page

1349 / 1358

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Tensile Strength
  • Platelet-Derived Growth Factor
  • Phenotype
  • Oncogene Proteins
  • Nerve Tissue Proteins
  • Mice
  • Immunology
  • Humans