Tags

Type your tag names separated by a space and hit enter

Transcription factor GATA-6 is expressed in quiescent myofibroblasts in idiopathic pulmonary fibrosis.
Am J Respir Cell Mol Biol. 2010 May; 42(5):626-32.AJ

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+Show Affiliations

Department of Medicine, Pulmonary Division, FI-00014 University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. outi.lepparanta@helsinki.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19597127

Citation

Leppäranta, Outi, et al. "Transcription Factor GATA-6 Is Expressed in Quiescent Myofibroblasts in Idiopathic Pulmonary Fibrosis." American Journal of Respiratory Cell and Molecular Biology, vol. 42, no. 5, 2010, pp. 626-32.
Leppäranta O, Pulkkinen V, Koli K, et al. Transcription factor GATA-6 is expressed in quiescent myofibroblasts in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol. 2010;42(5):626-32.
Leppäranta, O., Pulkkinen, V., Koli, K., Vähätalo, R., Salmenkivi, K., Kinnula, V. L., Heikinheimo, M., & Myllärniemi, M. (2010). Transcription factor GATA-6 is expressed in quiescent myofibroblasts in idiopathic pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology, 42(5), 626-32. https://doi.org/10.1165/rcmb.2009-0021OC
Leppäranta O, et al. Transcription Factor GATA-6 Is Expressed in Quiescent Myofibroblasts in Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2010;42(5):626-32. PubMed PMID: 19597127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcription factor GATA-6 is expressed in quiescent myofibroblasts in idiopathic pulmonary fibrosis. AU - Leppäranta,Outi, AU - Pulkkinen,Ville, AU - Koli,Katri, AU - Vähätalo,Riika, AU - Salmenkivi,Kaisa, AU - Kinnula,Vuokko L, AU - Heikinheimo,Markku, AU - Myllärniemi,Marjukka, Y1 - 2009/07/13/ PY - 2009/7/15/entrez PY - 2009/7/15/pubmed PY - 2010/5/1/medline SP - 626 EP - 32 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 42 IS - 5 N2 - 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. SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/19597127/Transcription_factor_GATA_6_is_expressed_in_quiescent_myofibroblasts_in_idiopathic_pulmonary_fibrosis_ L2 - https://www.atsjournals.org/doi/10.1165/rcmb.2009-0021OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -