RGD Reference Report - Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury. - Rat Genome Database

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Regulation of hepatocyte growth factor secretion by fibroblasts in patients with acute lung injury.

Authors: Quesnel, C  Marchand-Adam, S  Fabre, A  Marchal-Somme, J  Philip, I  Lasocki, S  Lecon, V  Crestani, B  Dehoux, M 
Citation: Quesnel C, etal., Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L334-43. Epub 2007 Dec 7.
RGD ID: 4142869
Pubmed: PMID:18065658   (View Abstract at PubMed)
DOI: DOI:10.1152/ajplung.00096.2007   (Journal Full-text)

The mechanisms of pulmonary repair in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are poorly known. Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are key factors involved in alveolar epithelial repair, present in the bronchoalveolar lavage fluid (BALF) from patients with ALI/ARDS. The role of BALF mediators in their production remains to be determined. We evaluated the overall effect of BALF from 52 patients (27 ventilated patients with ALI/ARDS, 10 ventilated patients without ALI, and 15 nonventilated control patients) on HGF and KGF synthesis by lung fibroblasts. Fibroblasts were cultured in the presence of BALF. HGF and KGF protein secretion was measured using ELISA, and mRNA expression was evaluated using quantitative real-time RT-PCR. Only BALF from ALI/ARDS patients upregulated both HGF and KGF mRNA expression and protein synthesis (+271 and +146% for HGF and KGF, respectively). BALF-induced HGF synthesis from ALI/ARDS patients was higher than that from ventilated patients without ALI (P < 0.05). HGF secretion was correlated with BALF IL-1beta levels (rho = 0.62, P < 0.001) and BALF IL-1beta/IL-1 receptor antagonist ratio (rho = 0.54, P < 0.007) in the ALI/ARDS group. An anti-IL-1beta antibody partially (>50%) inhibited the BALF-induced HGF and PGE(2) secretion, whereas NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, completely inhibited it. Anti-IL-1beta antibodies as well as NS-398 reversed the COX-2 upregulation induced by BALF. Therefore, IL-1beta is a main BALF mediator involved in HGF secretion, which is mediated through a PGE(2)/COX-2-dependent mechanism. BALF mediators may participate in vivo in the production of HGF and KGF by lung fibroblasts during ALI/ARDS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
adult respiratory distress syndrome  IEP 4142869protein:increased expression:lungRGD 
adult respiratory distress syndrome  ISOIL1B (Homo sapiens)4142869; 4142869protein:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1b  (interleukin 1 beta)

Genes (Mus musculus)
Il1b  (interleukin 1 beta)

Genes (Homo sapiens)
IL1B  (interleukin 1 beta)


Additional Information