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pubmed:abstractText |
The excessive matrix deposition in lung fibrosis is thought to be due to enhanced formation and activity of TGFbeta1, which stimulates synthesis and inhibits degradation of matrix proteins. The cellular mechanisms triggered by TGFbeta1 are still incompletely understood. Recently, a novel transcriptional target of TGFbeta1 has been identified, i.e. the human serum and glucocorticoid dependent kinase hSGK1. The present study has been performed to explore whether TGFbeta1 stimulates hSGK1 transcription in lung fibroblasts and whether lung fibrosis is associated with enhanced hSGK1 expression. As evident from Northern Blotting, TGFbeta1 strongly upregulates hSGK1 in human lung fibroblasts, an effect partially reversed by p38-kinase inhibitor SB203580. In situ hybridization experiments reveal that in intact lung tissue hSGK1 is expressed in single type II alveolar pneumocytes and macrophages. In contrast, in fibrotic lung tissue a dramatic upregulation of hSGK1 mRNA as well as a strong expression of hSGK1 protein is observed in epithelial cells and interstitial cells comprising macrophages and fibroblasts. In conclusion, in lung fibrosis, the serine/threonine kinase hSGK1 is upregulated, an effect at least partially accounted for by TGFbeta1. The full effect of TGFbeta1 requires the activation of p38 kinase.
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