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The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induces fibrosis

Fibrogenesis is usually initiated when regenerative processes have failed and/or chronic inflammation occurs. It is characterised by the activation of tissue fibroblasts and dysregulated synthesis of extracellular matrix proteins. FHL2 (four-and-a-half LIM domain protein 2) is a scaffolding protein that interacts with numerous cellular proteins, regulating signalling cascades and gene transcription. It is involved in tissue remodelling and tumour progression. Recent data suggest that FHL2 might support fibrogenesis by maintaining the transcriptional expression of alpha smooth muscle actin and the excessive synthesis and assembly of matrix proteins in activated fibroblasts. Here, we present evidence that FHL2 does not promote bleomycin-induced lung fibrosis, but rather suppresses this process by attenuating lung inflammation. Loss of FHL2 results in increased expression of the pro-inflammatory matrix protein tenascin C and downregulation of the macrophage activating C-type lectin receptor DC-SIGN. Consequently, FHL2 knockout mice developed a severe and long-lasting lung pathology following bleomycin administration due to enhanced expression of tenascin C and impaired activation of inflammation-resolving macrophages.

Titel: The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induces fibrosis
Verfasser: Alnajar, Abdulaleem GND
Nordhoff, Carolin GND
Schied, Tanja
Chiquet-Ehrismann, Ruth
Loser, Karin GND
Vogl, Thomas
Ludwig, Stephan
Wixler, Viktor GND
Organisation: FB 13: Biologie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 18.11.2013
Publikation in MIAMI: 19.02.2014
Datum der letzten Änderung: 10.09.2014
Quelle: PLoS ONE 8 (2013) 11, e81356
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 3.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2013/2014 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-44319594399
Permalink: http://nbn-resolving.de/urn:nbn:de:hbz:6-44319594399
DOI: 10.1371/journal.pone.0081356
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