Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis

Heat shock protein 27 (HSP27) is a member of the small molecular weight HSP family. Upon treatment with transforming growth factor β1 (TGF-β1), we observed upregulation of HSP27 along with that of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation, in cultured human and mouse l...

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Published in:PloS one Vol. 11; no. 2; p. e0148998
Main Authors: Park, Ah-Mee, Kanai, Kyosuke, Itoh, Tatsuki, Sato, Takao, Tsukui, Tatsuya, Inagaki, Yutaka, Selman, Moises, Matsushima, Kouji, Yoshie, Osamu
Format: Journal Article
Language:English
Published: United States Public Library of Science 09.02.2016
Public Library of Science (PLoS)
Subjects:
Actin
Actins - physiology
Aged
Alveoli
Animal tissues
Animals
Antibiotics
Biocompatibility
Biology and Life Sciences
Biomedical materials
Bleomycin
Bleomycin - pharmacology
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cell Line
Cell survival
Collagen (type I)
Collagen Type I - physiology
Differentiation
E-cadherin
Epithelial cells
Female
Fibroblasts
Fibroblasts - drug effects
Fibroblasts - physiology
Fibronectin
Fibronectins - physiology
Fibrosis
Gene Knockdown Techniques
Genetic aspects
Growth factors
Heat shock proteins
HSP27 Heat-Shock Proteins - physiology
Hsp27 protein
Humans
Idiopathic Pulmonary Fibrosis - physiopathology
Immunoglobulins
Kidneys
Localization
Lung diseases
Macrophages
Male
Medical prognosis
Medicine and Health Sciences
Mice
Molecular weight
Myofibroblasts - physiology
Osteopontin
Osteopontin - physiology
Physiological aspects
Polymerase Chain Reaction
Polymerization
Preventive medicine
Pulmonary fibrosis
Pulmonary Fibrosis - chemically induced
Pulmonary Fibrosis - physiopathology
Research and Analysis Methods
Respiratory tract
Risk factors
Rodents
siRNA
Smooth muscle
Transforming growth factor
Transforming Growth Factor beta1 - physiology
Transforming growth factor-b1
University faculty
Mexico
Japan
ISSN:1932-6203, 1932-6203
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Summary:Heat shock protein 27 (HSP27) is a member of the small molecular weight HSP family. Upon treatment with transforming growth factor β1 (TGF-β1), we observed upregulation of HSP27 along with that of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation, in cultured human and mouse lung fibroblasts. Furthermore, by using siRNA knockdown, we demonstrated that HSP27 was involved in cell survival and upregulation of fibronectin, osteopontin (OPN) and type 1 collagen, all functional markers of myofibroblast differentiation, in TGF-β1-treated MRC-5 cells. In lung tissues of bleomycin-treated mice, HSP27 was strongly upregulated and substantially co-localized with α-SMA, OPN and type I collagen but not with proSP-C (a marker of type II alveolar epithelial cells), E-cadherin (a marker of epithelial cells) or F4/80 (a marker of macrophages). A similar co-localization of HSP27 and α-SMA was observed in lung tissues of patients with idiopathic pulmonary fibrosis. Furthermore, airway delivery of HSP27 siRNA effectively suppressed bleomycin-induced pulmonary fibrosis in mice. Collectively, our findings indicate that HSP27 is critically involved in myofibroblast differentiation of lung fibroblasts and may be a promising therapeutic target for lung fibrotic diseases.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: AMP OY. Performed the experiments: AMP KK TI TT. Analyzed the data: AMP KK TI OY. Contributed reagents/materials/analysis tools: TS YI MS KM. Wrote the paper: AMP MS OY.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0148998