title: The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induced fibrosis.
abstract: 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.
authors.affiliation: Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Abdulaleem
authors.initials: A
authors.lastname: Alnajar
authors.forename: Carolin
authors.initials: C
authors.lastname: Nordhoff
authors.forename: Tanja
authors.initials: T
authors.lastname: Schied
authors.forename: Ruth
authors.initials: R
authors.lastname: Chiquet-Ehrismann
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Viktor
authors.initials: V
authors.lastname: Wixler
mesh_terms: D000818:Animals; D001761:Bleomycin; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D060850:LIM-Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019063:Tenascin / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D001761:Bleomycin; D015815:Cell Adhesion Molecules; D060850:LIM-Homeodomain Proteins; D037181:Lectins, C-Type; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D019063:Tenascin; D014157:Transcription Factors; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C491382:Fhl2 protein, mouse