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| Status |
Public on Mar 28, 2024 |
| Title |
Effects of Antifibrotic Drugs on Transcriptome of Peripheral Blood Mononuclear Cells in Idiopathic Pulmonary Fibrosis [IPF_PBMC] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Two antifibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells are immunocompetent cells that can predispose to those within the lungs and orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in bulk peripheral blood mononuclear cells of patients with IPF and the effects of antifibrotic drugs on these signatures. Differentially expressed genes (DEGs) were analyzed in patients with IPF and healthy controls, before and after antifibrotic treatment. Enrichment analysis suggested that fatty acid elongation interferes with profibrotic TGF-β/ signaling and production of oxidative stress since treatment with NTD upregulated the elongation enzymes ELOVL6 and ELOVL7. Treatment with PFD downregulated COL1A1 which produces wound-healing collagens, as activated monocyte-derived macrophages during tissue damage participate in the production of collagen, type I, and alpha 1. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinases activation, and inhibition of PAI-1 activity attenuates lung fibrosis. DEGs analysis suggested that both PFD and NTD upregulated SERPINE1 which in turn regulates PAI-1 activity. This study detected different DEGs as a result of PFD and NTD treatments, suggesting different mechanistic roles for the two antifibrotic drugs.
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| Overall design |
To investigate the pathogenesis of IPF in PBMCs, we compared IPF (n=6) and healthy control (n=6) samples by RNA-seq.
Then, to investigate the effects of antifibrotic drugs in PBMCs, we compared samples before and after administration of PFD (n=3) and NTD (n=3), respectively, by RNA-seq.
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| Contributor(s) |
Ishii D, Kawasaki T, Sato H, Tatsumi K, Imamoto T, Yoshioka K, Abe M, Hasegawa Y, Ohara O, Suzuki T |
| Citation missing |
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| Submission date |
Nov 22, 2023 |
| Last update date |
Mar 28, 2024 |
| Contact name |
Takeshi Kawasaki |
| E-mail(s) |
kawatake@chiba-u.jp
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| Phone |
+81-43-222-7171
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| Organization name |
Chiba University
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| Department |
Respirology
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| Street address |
1-8-1, Inohana, Chuoku
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| City |
Chiba |
| ZIP/Postal code |
2608670 |
| Country |
Japan |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA1044112 |
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