The in vivo fibrotic role of FIZZ1 in pulmonary fibrosis

FIZZ (found in inflammatory zone) 1, a member of a cysteine-rich secreted protein family, is highly induced in lung allergic inflammation and bleomycin induced lung fibrosis, and primarily expressed by airway and type II alveolar epithelial cells. This novel mediator is known to stimulate α-smooth m...

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Bibliographic Details
Published in:PloS one 2014-02, Vol.9 (2), p.e88362-e88362
Main Authors: Liu, Tianju, Yu, Hongfeng, Ullenbruch, Matthew, Jin, Hong, Ito, Toshihiro, Wu, Zhe, Liu, Jianhua, Phan, Sem H
Format: Article
Language:English
Subjects:
Actin
Adenoviridae - metabolism
Animals
B cells
Biology
Bleomycin
Bone marrow
Bone Marrow Cells - drug effects
Bone Marrow Cells - metabolism
Bone Marrow Cells - pathology
Cell Differentiation - drug effects
Collagen
Cysteine
Cytokines - metabolism
Dendritic cells
Epithelial cells
Fibroblasts
Fibrosis
Gene expression
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Green Fluorescent Proteins - metabolism
Hydroxyproline - metabolism
Hypersensitivity
Hypoxia
In vivo methods and tests
Inflammation
Intercellular Signaling Peptides and Proteins - deficiency
Intercellular Signaling Peptides and Proteins - metabolism
Kinases
Lung diseases
Macrophages - drug effects
Macrophages - metabolism
Macrophages - pathology
Medical schools
Medicine
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscles
Myofibroblasts - drug effects
Myofibroblasts - metabolism
Myofibroblasts - pathology
Pathology
Pulmonary fibrosis
Pulmonary Fibrosis - metabolism
Pulmonary Fibrosis - pathology
Rats
Respiratory tract
Rodents
Smooth muscle
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Summary:FIZZ (found in inflammatory zone) 1, a member of a cysteine-rich secreted protein family, is highly induced in lung allergic inflammation and bleomycin induced lung fibrosis, and primarily expressed by airway and type II alveolar epithelial cells. This novel mediator is known to stimulate α-smooth muscle actin and collagen expression in lung fibroblasts. The objective of this study was to investigate the in vivo effects of FIZZ1 on the development of lung fibrosis by evaluating bleomycin-induced pulmonary fibrosis in FIZZ1 deficient mice. FIZZ1 knockout mice exhibited no detectable abnormality. When these mice were treated with bleomycin they exhibited significantly impaired pulmonary fibrosis relative to wild type mice, along with impaired proinflammatory cytokine/chemokine expression. Deficient lung fibroblast activation was also noted in the FIZZ1 knockout mice. Moreover, recruitment of bone marrow-derived cells to injured lung was deficient in FIZZ1 knockout mice. Interestingly in vitro FIZZ1 was shown to have chemoattractant activity for bone marrow cells, including bone marrow-derived dendritic cells. Finally, overexpression of FIZZ1 exacerbated fibrosis. These findings suggested that FIZZ1 exhibited profibrogenic properties essential for bleomycin induced pulmonary fibrosis, as reflected by its ability to induce myofibroblast differentiation and recruit bone marrow-derived cells.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0088362