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PDGF-BB induces PRMT1 expression through ERK1/2 dependent STAT1 activation and regulates remodeling in primary human lung fibroblasts

Sun, Q. and Liu, L. and Mandal, J. and Molino, A. and Stolz, D. and Tamm, M. and Lu, S. and Roth, M.. (2016) PDGF-BB induces PRMT1 expression through ERK1/2 dependent STAT1 activation and regulates remodeling in primary human lung fibroblasts. Cellular Signalling, 28 (4). pp. 307-315.

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Official URL: https://edoc.unibas.ch/62426/

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Abstract

Tissue remodeling of sub-epithelial mesenchymal cells is a major pathology occurring in chronic obstructive pulmonary disease (COPD) and asthma. Fibroblasts, as a major source of interstitial connective tissue extracellular matrix, contribute to the fibrotic and inflammatory changes in these airways diseases. Previously, we described that protein arginine methyltransferase-1 (PRMT1) participates in airway remodeling in a rat model of pulmonary inflammation. In this study we investigated the mechanism by which PDGF-BB regulates PRMT1 in primary lung fibroblasts, isolated from human lung biopsies. Fibroblasts were stimulated with PDGF-BB for up-to 48h and the regulatory and activation of signaling pathways controlling PRMT1 expression were determined. PRMT1 was localized by immuno-histochemistry in human lung tissue sections and by immunofluorescence in isolated fibroblasts. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI1. ERK1/2 mitogen activated protein kinase (MAPK) was blocked by PD98059, p38 MAPK by SB203580, and STAT1 by small interference (si) RNA treatment. The results showed that PDGF-BB significantly increased PRMT1 expression after 1h lasting over 48h, through ERK1/2 MAPK and STAT1 signaling. The inhibition of ERK1/2 MAPK or of PRMT1 activity decreased PDGF-BB induced fibroblast proliferation, COX2 production, collagen-1A1 secretion, and fibronectin production. These findings suggest that PRMT1 is a central regulator of tissue remodeling and that the signaling sequence controlling its expression in primary human lung fibroblast is PDGF-ERK-STAT1. Therefore, PRMT1 presents a novel therapeutic and diagnostic target for the control of airway wall remodeling in chronic lung diseases.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Stolz)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Stolz)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Tamm)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Tamm)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
UniBasel Contributors:Roth-Chiarello, Michael and Tamm, Michael and Stolz, Daiana
Item Type:Article, refereed
Article Subtype:Research Article
e-ISSN:1873-3913
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:07 Jan 2019 19:08
Deposited On:07 Jan 2019 19:08

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