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Am J Physiol Lung Cell Mol Physiol (December 3, 2004). doi:10.1152/ajplung.00249.2004
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Submitted on July 2, 2004
Accepted on November 28, 2004

Defect of Hepatocyte Growth Factor production by fibroblasts in human pulmonary emphysema

Laurent Plantier1, Sylvain Marchand-Adam1, Joelle Marchal-Somme1, Guy Leseche2, Michel Fournier3, Monique Dehoux4, Michel Aubier5, and Bruno Crestani5*

1 INSERM U408, Faculte de Medecine Xavier Bichat, Paris, France
2 Service de Chirurgie thoracique, Hopital Beaujon, Clichy, France
3 Service de pneumologie, Hopital Beaujon, Clichy, France
4 INSERM U408, Faculte de Medecine Xavier Bichat, Paris, France; Service de Biochimie, Hopital Bichat, Paris, France
5 INSERM U408, Faculte de Medecine Xavier Bichat, Paris, France; Service de Pneumologie, Hopital Bichat, Paris, France

* To whom correspondence should be addressed. E-mail: bruno.crestani{at}bch.ap-hop-paris.fr.

Pulmonary emphysema results from an excessive degradation of lung parenchyma associated with a failure of alveolar repair. Secretion by pulmonary fibroblasts of the Hepatocyte growth factor (HGF) and the Keratinocyte growth factor (KGF) is crucial to an effective epithelial repair after lung injury. We hypothesized that abnormal HGF or KGF secretion by pulmonary fibroblasts could play a role in the development of emphysema. We measured in vitro production of HGF and KGF by human fibroblasts cultured from emphysematous and normal lung samples. HGF and KGF production was quantified at basal state and after stimulation. Intracellular content of HGF was lower in emphysema (1.52 pg/µg; 0.15-7.40) than in control fibroblasts (14.16pg/µg; 2.50-47.62; p=0.047). HGF production by emphysema fibroblasts (19.3 pg/µg protein [10.4-39.2]) was lower than that of controls at baseline (57.5 pg/Fg [20.4-116], p=0.019) and after stimulation with interleukin-1{beta} or prostaglandin E2. Neither retinoic acids (all-trans and 9-cis) nor N-acetyl-cysteine could reverse this abnormality. KGF production by emphysema fibroblasts (5.3 pg/µg [2.2-9.3]) was similar to that of controls at baseline (2.6 pg/µg [1-6.1], p=0.14) but could not be stimulated with interleukin-1{beta}. A decreased secretion of HGF by pulmonary fibroblasts could contribute to the insufficient alveolar repair in pulmonary emphysema.




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