| 19597127 |
Lepparanta O, Pulkkinen V, Koli K, Vahatalo R, Salmenkivi K, Kinnula VL, Heikinheimo M, Myllarniemi M: Transcription Factor GATA-6 is Expressed in Quiescent Myofibroblasts in Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2009 Jul 13.
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, 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-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 are negative for Ki67 and Caspase-3. Cultured human IPF/UIP fibroblasts expressed GATA-6 mRNA, whereas cells from the normal lung did not. In cultured A549 lung epithelial cells, the induction of GATA-6 by TGF-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 TGF-beta1. In conclusion, the hallmark of IPF/UIP histopathology, the fibroblast focus, consists of differentiated, quiescent cells that are prominently expressing GATA-6. |
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