Higher TRIP-1 level explains diminished collagen contraction ability of fetal versus adult fibroblasts.

Abstract

Acute lung injury involving extremely immature lungs often heals without excessive fibrosis unlike later in gestation and in adults. Several factors may be involved, but fibroblast contraction of collagen has been linked to the level of wound fibrosis. To assess whether human lung fibroblasts of fetal versus adult origin differ in ability to contract collagen and define the molecular underpinnings, we performed three-dimensional collagen contraction assay, analyzed their differential mRNA profile, specifically for transforming growth factor-beta (TGF-beta) signaling pathway and extracellular matrix components, studied the cell response to TGF-beta in culture, and used two-dimensional gel electrophoresis followed by mass spectrometry to identify differences in their overall proteomes. Human lung fetal fibroblasts contracted the collagen matrix less than the adults. Smooth muscle actin expression did not differ. TGF-beta stimulation resulted in greater Smad3 phosphorylation in fetal compared with adults. mRNA and proteomic profiling reveal a number of TGF-beta pathways, ECM components, and cytoskeletal regulatory molecules are differentially expressed between the cell types. Of note is TGF-beta receptor interacting protein 1 (TRIP-1), which we show inhibits fibroblast collagen contraction and is higher in fetal than adult fibroblasts. We conclude that human lung fetal fibroblasts are less able to contract collagen than adult lung fibroblasts. The diminished ability is not due to impediment of Smad3 activation but rather, at least in part, due to their higher level of TRIP-1 expression. TRIP-1 is a novel modulator of fibroblast collagen contraction.

• Authors: Angels Navarro, Mo Rezaiekhaligh, J Andrew Keightley, Sherry M Mabry, Ricardo E Perez, Ikechukwu I Ekekezie
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 296 Issue 6 Pg. L928-35 (Jun 2009) ISSN: 1040-0605 [Print] United States
• PMID: 19329541 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Eukaryotic Initiation Factor-3
• SMAD3 protein, human
• Smad3 Protein
• Transforming Growth Factor beta
• EIF3I protein, human

Topics

• Adult
• Cells, Cultured
• Collagen Type I (physiology)
• Electrophoresis, Gel, Two-Dimensional
• Eukaryotic Initiation Factor-3 (genetics, metabolism)
• Fetus (cytology)
• Fibroblasts (cytology, drug effects, physiology)
• Gene Expression Regulation, Developmental
• Humans
• Lung (cytology, embryology, metabolism)
• Proteomics
• Pulmonary Fibrosis (metabolism, pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta (pharmacology)
• Wound Healing (physiology)