Different effects of growth factors on proliferation and matrix production of normal and fibrotic human lung fibroblasts

In idiopathic pulmonary fibrosis (IPF), proliferation of fibroblasts and increased matrix deposition result in pulmonary damage and respiratory insufficiency. We cultured human fibroblasts from lung biopsies of healthy adults and of three patients with IPF (histologically usual interstital pneumonit...

Full description

Saved in:
Bibliographic Details
Published in:Lung 2005-08, Vol.183 (4), p.225-237
Main Authors: Hetzel, M, Bachem, M, Anders, D, Trischler, G, Faehling, M
Format: Article
Language:English
Subjects:
Actins - metabolism
Care and treatment
Cell Proliferation - drug effects
Cytokines
Diagnosis
Extracellular Matrix Proteins - metabolism
Fibroblasts - drug effects
Fibroblasts - physiology
Fibronectins - metabolism
Fluorescent Antibody Technique
Growth Substances - pharmacology
Health aspects
Humans
Lungs
Peptides
Pulmonary fibrosis
Pulmonary Fibrosis - pathology
Pulmonary Fibrosis - physiopathology
Respiratory diseases
Respiratory system
Transforming growth factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In idiopathic pulmonary fibrosis (IPF), proliferation of fibroblasts and increased matrix deposition result in pulmonary damage and respiratory insufficiency. We cultured human fibroblasts from lung biopsies of healthy adults and of three patients with IPF (histologically usual interstital pneumonitis, UIP) in order to compare proliferation ([(3)H]thymidine incorporation, cell count) and matrix protein expression (immune fluorescence, quantification of fibronectin synthesis using time-resolved immune fluorescence) of normal and UIP fibroblasts in response to various growth factors. The growth factors platelet-derived growth factor-BB (PDGF), epidermal growth factor (EGF), insulin growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), tumor necrosis factor alpha (TNFalpha), Transforming growth factor-beta (TGFbeta(1)), and fibroblast growth factor-2 (FGF-2) stimulate proliferation of normal lung fibroblasts significantly more than proliferation of UIP fibroblasts. Immunofluorescence reveals extensive expression of collagen I, collagen III, and fibronectin induced by serum, TGFbeta(1), and TNFalpha. This expression is more pronounced in UIP fibroblasts than in normal fibroblasts. Quantification of fibronectin synthesis reveals an enhanced fibronectin synthesis by UIP fibroblasts in response to PDGF, EGF, IGF-1, IGF-2, TNFalpha, TGFbeta(1), and FGF-2). Fibroblasts from normal and UIP lungs differ in their response to growth factors: Whereas normal fibroblasts show a predominantly proliferative response, UIP fibroblasts show an enhanced synthetic activity. Different fibroblast responses may contribute to progressive pulmonary fibrosis in patients with UIP.
ISSN:0341-2040
1432-1750
DOI:10.1007/s00408-004-2534-z