Smooth muscle αv integrins regulate vascular fibrosis via CD109 downregulation of TGF-β signalling

التفاصيل البيبلوغرافية
العنوان: Smooth muscle αv integrins regulate vascular fibrosis via CD109 downregulation of TGF-β signalling
المؤلفون: Li, Zhenlin, Belozertseva, Ekaterina, Parlakian, Ara, Bascetin, Rümeyza, Louis, Huguette, Kawamura, Yuki, Blanc, Jocelyne, Gao-Li, Jacqueline, Pinet, Florence, Lacy-Hulbert, Adam, Challande, Pascal, Humphrey, Jay, Regnault, Veronique, Lacolley, Patrick
المساهمون: Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing B2A, Défaillance Cardiovasculaire Aiguë et Chronique DCAC, Yale University New Haven, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 RID-AGE, University of Washington Seattle, Institut Jean Le Rond d'Alembert DALEMBERT
بيانات النشر: Oxford University Press on behalf of the European Society of Cardiology
سنة النشر: 2023
المجموعة: LillOA (Lille Open Archive - Université de Lille)
مصطلحات موضوعية: Alpha v integrin, Vascular smooth muscle cell, Collagen, CD109
الوصف: Aims αv integrins are implicated in fibrosis in a number of organs through their ability to activate TGF-β. However their role in vascular fibrosis and collagen accumulation is only partially understood. Here we have used αv conditional knockout mice and cell lines to determine how αv contributes to vascular smooth muscle cell (VSMC) function in vascular fibrosis and the role of TGF-β in that process. Methods and results Angiotensin II (Ang II) treatment causes upregulation of αv and β3 expression in the vessel wall, associated with increased collagen deposition. We found that deletion of αv integrin subunit from VSMCs (αvSMKO) protected mice against angiotensin II-induced collagen production and assembly. Transcriptomic analysis of the vessel wall in αvSMKO mice and controls identified a significant reduction in expression of fibrosis and related genes in αvSMKO mice. In contrast, αvSMKO mice showed prolonged expression of CD109, which is known to affect TGF-β signalling. Using cultured mouse and human VSMCs, we showed that overexpression of CD109 phenocopied knockdown of αv integrin, attenuating collagen expression, TGF-β activation, and Smad2/3 signalling in response to angiotensin II or TGF-β stimulation. CD109 and TGF-β receptor were internalized in early endosomes. Conclusion We identify a role for VSMC αv integrin in vascular fibrosis and show that αv acts in concert with CD109 to regulate TGF-β signalling. ; 3 ; 2
نوع الوثيقة: other/unknown material
وصف الملف: application/octet-stream
اللغة: English
العلاقة: Combattre l'insuffisance cardiaque; Intégrines alphav des cellules musculaires lisses vasculaires : liens mécanistiques entre rigidité artérielle et génération de thrombine intrapariétale; European Heart Journal Open; http://hdl.handle.net/20.500.12210/96308Test
الإتاحة: https://doi.org/20.500.12210/96308Test
https://hdl.handle.net/20.500.12210/96308Test
حقوق: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.93025806
قاعدة البيانات: BASE