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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Vydané v:	PloS one Ročník 11; číslo 2; s. e0148998
Hlavní autori:	Park, Ah-Mee, Kanai, Kyosuke, Itoh, Tatsuki, Sato, Takao, Tsukui, Tatsuya, Inagaki, Yutaka, Selman, Moises, Matsushima, Kouji, Yoshie, Osamu
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 09.02.2016 Public Library of Science (PLoS)
Predmet:	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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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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