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Effects of Anti-Fibrotic Drugs on Transcriptome of Peripheral Blood Mononuclear Cells in Idiopathic Pulmonary Fibrosis.
Ishii, Daisuke; Kawasaki, Takeshi; Sato, Hironori; Tatsumi, Koichiro; Imamoto, Takuro; Yoshioka, Keiichiro; Abe, Mitsuhiro; Hasegawa, Yoshinori; Ohara, Osamu; Suzuki, Takuji.
Afiliación
  • Ishii D; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Kawasaki T; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Sato H; Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Tatsumi K; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Imamoto T; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Yoshioka K; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Abe M; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Hasegawa Y; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba 292-0818, Japan.
  • Ohara O; Department of Applied Genomics, Kazusa DNA Research Institute, Chiba 292-0818, Japan.
  • Suzuki T; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Int J Mol Sci ; 25(7)2024 Mar 28.
Article en En | MEDLINE | ID: mdl-38612561
ABSTRACT
Two anti-fibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells (PBMCs) are immunocompetent cells that could orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in the bulk PBMCs of patients with IPF and the effects of anti-fibrotic drugs on these signatures. Differentially expressed genes (DEGs) between "patients with IPF and healthy controls" and "before and after anti-fibrotic treatment" were analyzed. Enrichment analysis suggested that fatty acid elongation interferes with TGF-ß/Smad signaling and the production of oxidative stress since treatment with NTD upregulates the fatty acid elongation enzymes ELOVL6. Treatment with PFD downregulates COL1A1, which produces wound-healing collagens because activated monocyte-derived macrophages participate in the production of collagen, type I, and alpha 1 during tissue damage. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinase activation, and the inhibition of PAI-1 activity attenuates lung fibrosis. DEG analysis suggested that both the PFD and NTD upregulate SERPINE1, which regulates PAI-1 activity. This study embraces a novel approach by using RNA sequencing to examine PBMCs in IPF, potentially revealing systemic biomarkers or pathways that could be targeted for therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidor 1 de Activador Plasminogénico / Fibrosis Pulmonar Idiopática Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidor 1 de Activador Plasminogénico / Fibrosis Pulmonar Idiopática Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza