دورية أكاديمية
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TGF-β1, pSmad-2/3, Smad-7, and β-Catenin Are Augmented in the Pulmonary Arteries from Patients with Idiopathic Pulmonary Fibrosis (IPF): Role in Driving Endothelial-to-Mesenchymal Transition (EndMT).

التفاصيل البيبلوغرافية
العنوان: TGF-β1, pSmad-2/3, Smad-7, and β-Catenin Are Augmented in the Pulmonary Arteries from Patients with Idiopathic Pulmonary Fibrosis (IPF): Role in Driving Endothelial-to-Mesenchymal Transition (EndMT).
المؤلفون: Gaikwad AV; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; National Health and Medical Research Council (NHMRC) Centre of Research Excellence (CRE) in Pulmonary Fibrosis, Respiratory Medicine and Sleep Unit, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia., Eapen MS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; National Health and Medical Research Council (NHMRC) Centre of Research Excellence (CRE) in Pulmonary Fibrosis, Respiratory Medicine and Sleep Unit, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia., Dey S; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia., Bhattarai P; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia., Shahzad AM; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia., Chia C; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; Launceston Respiratory and Sleep Centre, Launceston, TAS 7250, Australia.; Department of Respiratory Medicine, Launceston General Hospital, Launceston, TAS 7250, Australia., Jaffar J; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC 3004, Australia.; Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia., Westall G; Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC 3004, Australia.; Department of Immunology and Pathology, Monash University, Melbourne, VIC 3004, Australia., Sutherland D; Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.; Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada., Singhera GK; Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.; Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada., Hackett TL; Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.; Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada., Lu W; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; National Health and Medical Research Council (NHMRC) Centre of Research Excellence (CRE) in Pulmonary Fibrosis, Respiratory Medicine and Sleep Unit, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.; Launceston Respiratory and Sleep Centre, Launceston, TAS 7250, Australia., Sohal SS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS 7248, Australia.; National Health and Medical Research Council (NHMRC) Centre of Research Excellence (CRE) in Pulmonary Fibrosis, Respiratory Medicine and Sleep Unit, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.; Launceston Respiratory and Sleep Centre, Launceston, TAS 7250, Australia.
المصدر: Journal of clinical medicine [J Clin Med] 2024 Feb 19; Vol. 13 (4). Date of Electronic Publication: 2024 Feb 19.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101606588 Publication Model: Electronic Cited Medium: Print ISSN: 2077-0383 (Print) Linking ISSN: 20770383 NLM ISO Abbreviation: J Clin Med Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, [2012]-
مستخلص: Background: We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim to quantify drivers of EndMT in IPF patients compared to normal controls (NCs). Methods: Lung resections from thirteen IPF patients and eleven NCs were immunohistochemically stained for EndMT drivers, including TGF-β1, pSmad-2/3, Smad-7, and β-catenin. Intima, media, and adventitia were analysed for expression of each EndMT driver in pulmonary arteries. Computer- and microscope-assisted Image ProPlus7.0 image analysis software was used for quantifications. Results: Significant TGF-β1, pSmad-2/3, Smad-7, and β-catenin expression was apparent across all arterial sizes in IPF ( p < 0.05). Intimal TGF-β1, pSmad-2/3, Smad-7, and β-catenin were augmented in the arterial range of 100-1000 μm ( p < 0.001) compared to NC. Intimal TGF-β1 and β-catenin percentage expression showed a strong correlation with the percentage expression of intimal vimentin (r' = 0.54, p = 0.05 and r' = 0.61, p = 0.02, respectively) and intimal N-cadherin (r' = 0.62, p = 0.03 and r' = 0.70, p = 0.001, respectively). Intimal TGF-β1 and β-catenin expression were significantly correlated with increased intimal thickness as well (r' = 0.52, p = 0.04; r' = 0.052, p = 0.04, respectively). Moreover, intimal TGF-β1 expression was also significantly associated with increased intimal elastin deposition (r' = 0.79, p = 0.002). Furthermore, total TGF-β1 expression significantly impacted the percentage of DLCO (r' = -0.61, p = 0.03). Conclusions: This is the first study to illustrate the involvement of active TGF-β/Smad-2/3-dependent and β-catenin-dependent Wnt signalling pathways in driving EndMT and resultant pulmonary arterial remodelling in patients with IPF. EndMT is a potential therapeutic target for vascular remodelling and fibrosis in general in patients with IPF.
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معلومات مُعتمدة: Lung Foundation Australia; Clifford Craig Foundation Launceston General Hospital
فهرسة مساهمة: Keywords: endothelial-to-mesenchymal transition; idiopathic pulmonary fibrosis; pulmonary artery; pulmonary hypertension; vascular remodelling
تواريخ الأحداث: Date Created: 20240224 Latest Revision: 20240227
رمز التحديث: 20240227
مُعرف محوري في PubMed: PMC10888973
DOI: 10.3390/jcm13041160
PMID: 38398472
قاعدة البيانات: MEDLINE
الوصف
تدمد:2077-0383
DOI:10.3390/jcm13041160