Transcription factor GATA-6 is expressed in quiescent myofibroblasts in idiopathic pulmonary fibrosis
| Autor: | Ville Pulkkinen, Katri Koli, Kaisa Salmenkivi, Vuokko L. Kinnula, Markku Heikinheimo, Riika Vähätalo, Outi Leppäranta, Marjukka Myllärniemi |
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| Rok vydání: | 2009 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adult Pathology medicine.medical_specialty Cellular differentiation Clinical Biochemistry Apoptosis Epithelium Mesoderm Transforming Growth Factor beta1 Idiopathic pulmonary fibrosis Usual interstitial pneumonia Cell Line Tumor GATA6 Transcription Factor Pulmonary fibrosis medicine Humans RNA Messenger Fibroblast Molecular Biology Lung Cell Proliferation biology Cell Differentiation Cell Biology Transforming growth factor beta respiratory system Fibroblasts medicine.disease Actins Idiopathic Pulmonary Fibrosis respiratory tract diseases DNA-Binding Proteins Protein Transport medicine.anatomical_structure Gene Expression Regulation biology.protein Myofibroblast Biomarkers Transcription Factors |
| Zdroj: | American journal of respiratory cell and molecular biology. 42(5) |
| ISSN: | 1535-4989 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial pneumonia [UIP]) is a progressive disease with poor prognosis. Characteristic features of IPF/UIP include fibroblastic foci, which are patchy lesions of focal, disarranged myofibroblasts. GATA-6 is a transcription factor linked with cell differentiation. Its role in the development of IPF has not previously been investigated. We hypothesized that GATA-6 participates in the differentiation of fibroblasts into myofibroblasts in IPF/UIP lungs. The expression patterns of GATA-6, the mesenchymal marker alpha-smooth muscle actin (alpha-SMA), and markers for proliferation (Ki67) and apoptosis (caspase-3) were analyzed in human IPF/UIP tissue samples. The effects of GATA-6 overexpression and silencing were studied in cell cultures. The results show that the alpha-SMA-positive fibroblastic foci in IPF/UIP lungs are positive for GATA-6, but negative for Ki67 and caspase-3. Cultured human IPF/UIP fibroblasts expressed GATA-6 mRNA, whereas cells from the normal adult lung did not. In cultured A549 lung epithelial cells, the induction of GATA-6 by transforming growth factor-beta1 resulted in simultaneous expression of alpha-SMA and decrease of E-cadherin. The inhibition of GATA-6 expression in fibroblasts showed that GATA-6 mediates the alpha-SMA-inducing signal of transforming growth factor-beta1. In conclusion, the hallmark of IPF/UIP histopathology, the fibroblast focus, consists of differentiated, quiescent cells that prominently express GATA-6. |
| Databáze: | OpenAIRE |
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