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Original article (peer-reviewed)

Journal The Journal of Immunology
Volume (Issue) 202(1)
Page(s) 37 - 47
Title of proceedings The Journal of Immunology
DOI 10.4049/jimmunol.1800782

Open Access

Type of Open Access Publisher (Gold Open Access)


Tissue remodeling of subepithelial mesenchymal cells is a major pathologic condition of chronic obstructive pulmonary disease and asthma. Fibroblasts contribute to fibrotic events and inflammation in both airway diseases. Recent mechanistic studies established a link between mitochondrial dysfunction or aberrant biogenesis leading to tissue remodeling of the airway wall in asthma. Protein arginine methyltransferase-1 (PRMT1) participated in airway wall remodeling in pulmonary inflammation. This study investigated the mechanism by which PRMT1 regulates mitochondrial mass in primary human airway wall fibroblasts. Fibroblasts from control or asthma patients were stimulated with TGF-b for up to 48 h, and the signaling pathways controlling PRMT1 expression and mitochondrial mass were analyzed. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI-1. The SMAD2/3 pathway was blocked by SB203580 and C/EBPb by small interference RNA treatment. The data obtained from unstimulated cells showed a significantly higher basal expression of PRMT1 and mitochondrial markers in asthmatic compared with control fibroblasts. In all cells, TGF-b significantly increased the expression of PRMT1 through SMAD2/3 and C/EBPb. Subsequently, PRMT1 upregulated the expression of the mitochondria regulators PGC-1a and heat shock protein 60. Both the inhibition of the SAMD2/3 pathway or PRMT1 attenuated TGF-b–induced mitochondrial mass and C/EBPb and a-SMA expression. These findings suggest that the signaling sequence controlling mitochondria in primary human lung fibroblasts is as follows: TGF-b→SMAD2/3→C/EBPb→PRMT1→PGC-1a. Therefore, PRMT1 and C/EBPb present a novel Immunology,therapeutic and diagnostic target for airway wall remodeling in chronic lung diseases. The Journal of Immunology 2019, 202: 37–47.