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Constitutive high expression of protein arginine methyltransferase 1 in asthmatic airway smooth muscle cells is caused by reduced microRNA-19a expression and leads to enhanced remodeling.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2016
Author Sun Qingzhu, Liu Li, Wang Hui, Mandal Jyotshna, Khan Petra, Hostettler Katrin E, Stolz Daiana, Tamm Michael, Molino Antonio, Lardinois Didier, Lu Shemin, Roth Michael,
Project The vicious-cycle of acute exacerbation in chronic obstructive pulmonary disease: orchestration of infection, systemic inflammatory response and airway remodelling
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Original article (peer-reviewed)

Journal The Journal of allergy and clinical immunology
Page(s) in press - in press
Title of proceedings The Journal of allergy and clinical immunology
DOI 10.1016/j.jaci.2016.11.013


In asthma remodeling airway smooth muscle cells (ASMCs) contribute to airway wall thickness through increased proliferation, migration, and extracellular matrix deposition. Previously, we described that protein arginine methyltransferase 1 (PRMT1) participates in airway remodeling in pulmonary inflammation in E3 rats. We sought to define the asthma-specific regulatory mechanism of PRMT1 in human ASMCs. ASMCs from healthy subjects and asthmatic patients were activated with platelet-derived growth factor (PDGF)-BB. PRMT1 was localized by means of immunohistochemistry in human lung tissue sections and by means of immunofluorescence in isolated ASMCs. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI-1, signal transducer and activator of transcription 1 (STAT1) was suppressed by small interfering RNA, and extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) was suppressed by PD98059. MicroRNAs (miRs) were assessed by using real-time quantitative PCR and regulated by miR mimics or inhibitors. PRMT1 expression was significantly increased in lung tissue sections and in isolated ASMCs of patients with severe asthma. PDGF-BB significantly increased PRMT1 expression through ERK1/2 MAPK and STAT1 signaling in control ASMCs, whereas in ASMCs from asthmatic patients, these proteins were constitutively expressed. ASMCs from asthmatic patients had reduced miR-19a expression, causing upregulation of ERK1/2 MAPK, STAT1, and PRMT1. Inhibition of PRMT1 abrogated collagen type I and fibronectin deposition, cell proliferation, and migration of ASMCs from asthmatic patients. PRMT1 is a central regulator of tissue remodeling in ASMCs from asthmatic patients through the pathway: PDGF-BB-miR-19a-ERK1/2 MAPK and STAT1. Low miR-19a expression in ASMCs from asthmatic patients is the key event that results in constitutive increased PRMT1 expression and remodeling. Therefore PRMT1 is an attractive target to limit airway wall remodeling in asthmatic patients.