Transforming growth factor β1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis

Thomas J. Broekelmann, Andrew Harold Limper, Thomas V. Colby, John A. Mcdonald

Research output: Contribution to journalArticle

626 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, we demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, we now demonstrate the presence of transforming growth factor β1 (TGF-β1), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-β1 may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-β1 is the alveolar macrophage, and we demonstrate the expression of abundant TGF-β1 mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis.

Original languageEnglish (US)
Pages (from-to)6642-6646
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number15
StatePublished - Aug 1 1991

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Pulmonary Fibrosis
Transforming Growth Factors
Idiopathic Pulmonary Fibrosis
Extracellular Matrix
Connective Tissue
Gene Expression
Alveolar Macrophages
Fibroblasts
Procollagen
Lung
Fibronectins
Respiratory Insufficiency
Wound Healing
Cicatrix
In Situ Hybridization
Smooth Muscle
Actins
Immunohistochemistry
Air
Cytokines

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Transforming growth factor β1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. / Broekelmann, Thomas J.; Limper, Andrew Harold; Colby, Thomas V.; Mcdonald, John A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 15, 01.08.1991, p. 6642-6646.

Research output: Contribution to journalArticle

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