title: The in vivo fibrotic role of FIZZ1 in pulmonary fibrosis.
abstract: 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.
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Tianju
authors: T
authors: Liu
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Hongfeng
authors: H
authors: Yu
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Matthew
authors: M
authors: Ullenbruch
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Hong
authors: H
authors: Jin
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Toshihiro
authors: T
authors: Ito
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Zhe
authors: Z
authors: Wu
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Jianhua
authors: J
authors: Liu
authors: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors: Sem H
authors: SH
authors: Phan
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D001761:Bleomycin; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D051381:Rats
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C413576:Retnla protein, mouse; D001761:Bleomycin; D049452:Green Fluorescent Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006909:Hydroxyproline