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Lung

, Volume 183, Issue 4, pp 225–237 | Cite as

Different Effects of Growth Factors on Proliferation and Matrix Production of Normal and Fibrotic Human Lung Fibroblasts

  • M. Hetzel
  • M. Bachem
  • D. Anders
  • G. Trischler
  • M. Faehling
Article

Abstract

Objectives and methods: 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 ([3H]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. Findings: 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 α (TNFα), Transforming growth factor-β (TGFβ1), 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, TGFβ1, and TNFα. 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, TNFα, TGFβ1, and FGF-2). Conclusions: 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.

Keywords

Pulmonary fibrogenesis TNFα TGFβ UIP 

Abbreviations

EGF

epidermal growth factor

FGF-2

fibroblast growth factor-2 (basic fibroblast growth factor)

IGF-1

insulin-like growth factor-1

IGF-2

insulin-like growth factor-2

IPF

idiopathic pulmonary fibrosis

PDGF

platelet-derived growth factor-BB

SMC

smooth muscle cell

TGFβ1

transforming growth factor-β1

TNFα

tumor necrosis factor α

UIP

usual interstitial pneumonitis

UIP fibroblasts

human lung fibroblasts derived from UIP lungs

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • M. Hetzel
    • 1
  • M. Bachem
    • 2
  • D. Anders
    • 1
  • G. Trischler
    • 1
  • M. Faehling
    • 1
  1. 1.Abt. Innere Medizin IIUniversitätsklinikumGermany
  2. 2.Abt. Klinische Chemie und PathobiochemieUniversitätsklinikumGermany

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