دورية أكاديمية
أعرض في EDS

Sine oculis homeobox homolog 1 plays a critical role in pulmonary fibrosis.

التفاصيل البيبلوغرافية
العنوان: Sine oculis homeobox homolog 1 plays a critical role in pulmonary fibrosis.
المؤلفون: Wilson C; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Mertens TC; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Shivshankar P; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Bi W; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Collum SD; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Wareing N; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Ko J; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Weng T; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA., Naikawadi RP; Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, California, USA., Wolters PJ; Pulmonary, Critical Care, Allergy and Sleep Medicine, UCSF, San Francisco, California, USA., Maire P; Université de Paris Cité, Institut Cochin, INSERM, CNRS, Paris, France., Jyothula SS; Divisions of Critical Care, Pulmonary and Sleep Medicine, Department of Internal Medicine, McGovern Medical School, UTHealth, Houston, Texas, USA., Thandavarayan RA; Methodist J.C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, Texas, USA., Ren D; Methodist J.C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, Texas, USA., Elrod ND; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA., Wagner EJ; Department of Biochemistry and Biophysics, Center for RNA Biology, Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, KMRB G.9629, Rochester, New York, USA., Huang HJ; Methodist J.C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, Texas, USA., Dickey BF; Department of Pulmonary Medicine, Division of Internal Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA., Ford HL; Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA., Karmouty-Quintana H; Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth Houston), Houston, Texas, USA.; Divisions of Critical Care, Pulmonary and Sleep Medicine, Department of Internal Medicine, McGovern Medical School, UTHealth, Houston, Texas, USA.
المصدر: JCI insight [JCI Insight] 2022 May 23; Vol. 7 (10). Date of Electronic Publication: 2022 May 23.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
مواضيع طبية MeSH: Homeodomain Proteins*/genetics , Homeodomain Proteins*/metabolism , Idiopathic Pulmonary Fibrosis*/chemically induced , Idiopathic Pulmonary Fibrosis*/genetics, Animals ; Fibrosis ; Genes, Homeobox ; Mice ; Transcription Factors/genetics
مستخلص: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. The role of the developmental transcription factor Sine oculis homeobox homolog 1 (SIX1) in the pathophysiology of lung fibrosis is not known. IPF lung tissue samples and IPF-derived alveolar type II cells (AT2) showed a significant increase in SIX1 mRNA and protein levels, and the SIX1 transcriptional coactivators EYA1 and EYA2 were elevated. Six1 was also upregulated in bleomycin-treated (BLM-treated) mice and in a model of spontaneous lung fibrosis driven by deletion of Telomeric Repeat Binding Factor 1 (Trf1) in AT2 cells. Conditional deletion of Six1 in AT2 cells prevented or halted BLM-induced lung fibrosis, as measured by a significant reduction in histological burden of fibrosis, reduced fibrotic mediator expression, and improved lung function. These effects were associated with increased macrophage migration inhibitory factor (MIF) in lung epithelial cells in vivo following SIX1 overexpression in BLM-induced fibrosis. A MIF promoter-driven luciferase assay demonstrated direct binding of Six1 to the 5'-TCAGG-3' consensus sequence of the MIF promoter, identifying a likely mechanism of SIX1-driven MIF expression in the pathogenesis of lung fibrosis and providing a potentially novel pathway for targeting in IPF therapy.
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معلومات مُعتمدة: R01 HL139897 United States HL NHLBI NIH HHS; R01 HL157100 United States HL NHLBI NIH HHS; R01 HL138510 United States HL NHLBI NIH HHS; R01 HL129795 United States HL NHLBI NIH HHS; F30 HL147508 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Fibrosis; Pulmonology
المشرفين على المادة: 0 (Homeodomain Proteins)
0 (Transcription Factors)
تواريخ الأحداث: Date Created: 20220414 Date Completed: 20220524 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC9220956
DOI: 10.1172/jci.insight.142984
PMID: 35420997
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-3708
DOI:10.1172/jci.insight.142984