Transcription factor GATA-6 is expressed in quiescent myofibroblasts in idiopathic pulmonary fibrosis.

Abstract

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.

• Authors: Outi Leppäranta, Ville Pulkkinen, Katri Koli, Riika Vähätalo, Kaisa Salmenkivi, Vuokko L Kinnula, Markku Heikinheimo, Marjukka Myllärniemi
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 42 Issue 5 Pg. 626-32 (May 2010) ISSN: 1535-4989 [Electronic] United States
• PMID: 19597127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Biomarkers
• DNA-Binding Proteins
• GATA6 Transcription Factor
• GATA6 protein, human
• RNA, Messenger
• Transcription Factors
• Transforming Growth Factor beta1
• ZFPM2 protein, human

Topics

• Actins (metabolism)
• Adult
• Apoptosis (drug effects)
• Biomarkers (metabolism)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA-Binding Proteins (metabolism)
• Epithelium (drug effects, metabolism, pathology)
• Fibroblasts (drug effects, metabolism, pathology)
• GATA6 Transcription Factor (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Idiopathic Pulmonary Fibrosis (metabolism, pathology)
• Lung (drug effects, metabolism, pathology)
• Mesoderm (drug effects, metabolism, pathology)
• Protein Transport (drug effects)
• RNA, Messenger (genetics, metabolism)
• Transcription Factors (metabolism)
• Transforming Growth Factor beta1 (pharmacology)