Functional analysis of human fibrocytes derived from monocytes reveals their profibrotic phenotype through paracrine effects
Autor: | Kazuya Koyama, Kozo Kagawa, Shuichi Abe, Naoki Takahashi, Hiroshi Kawano, Yasuhiko Nishioka, Momoyo Azuma, Masami Kishi, Yoshinori Aono, Seidai Sato |
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Rok vydání: | 2020 |
Předmět: |
Pathology
medicine.medical_specialty Becaplermin General Biochemistry Genetics and Molecular Biology Monocytes 03 medical and health sciences Idiopathic pulmonary fibrosis Paracrine signalling 0302 clinical medicine Fibrocyte Pulmonary fibrosis medicine Humans Fibroblast Myofibroblasts Lung Cells Cultured biology business.industry Cell Differentiation General Medicine respiratory system Fibroblasts medicine.disease Idiopathic Pulmonary Fibrosis respiratory tract diseases medicine.anatomical_structure 030228 respiratory system 030220 oncology & carcinogenesis biology.protein Fibroblast Growth Factor 2 business Transcriptome Myofibroblast Platelet-derived growth factor receptor |
Zdroj: | The journal of medical investigation : JMI. 67(1.2) |
ISSN: | 1349-6867 |
Popis: | Fibrocytes, which are bone marrow-derived collagen-producing cells, were reported to play a role in the pathogenesis of pulmonary fibrosis. However, their function in pulmonary fibrosis is unclear. We analyzed their function compared with that of monocytes and localization in fibrotic tissues in patients with idiopathic pulmonary fibrosis (IPF). We compared the gene expression profile of monocyte-derived fibrocytes with that of monocytes by microarray analysis. Proliferation and differentiation into myofibroblasts were examined by 3H-thymidine incorporation assay and Western blotting. We measured the level of growth factors in the culture supernatant of fibrocytes by ELISA. The localization of fibrocytes in lung tissues of patients with IPF was determined by immunofluorescence staining. Compared with monocytes, fibrocytes had higher expression of extracellular matrix- and growth factor-encoding genes, including PDGF-B, FGF-2 and VEGF-B. Although fibrocytes did not proliferate in response to PDGF, co-culture of fibrocytes stimulated the growth of lung fibroblasts through the production of PDGF-BB. In the lung of IPF patients, CD45+Collagen-I+FSP-1+ cells, which have a similar phenotype to fibrocytes, were detected and co-stained with anti-PDGF antibody. This study suggested that fibrocytes function in pulmonary fibrosis partly by producing PDGF in the lungs of IPF patients. J. Med. Invest. 67 : 102-112, February, 2020. |
Databáze: | OpenAIRE |
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