P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype.
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
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
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
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
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