Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis
| Autor: | Kouji Matsushima, Yutaka Inagaki, Takao Sato, Ah-Mee Park, Tatsuki Itoh, Tatsuya Tsukui, Kyosuke Kanai, Moisés Selman, Osamu Yoshie |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology Pulmonary Fibrosis Cellular differentiation HSP27 Heat-Shock Proteins lcsh:Medicine Biochemistry Polymerase Chain Reaction Heat Shock Response Epithelium Mice Idiopathic pulmonary fibrosis 0302 clinical medicine Animal Cells Fibrosis Pulmonary fibrosis Medicine and Health Sciences Small interfering RNAs Osteopontin lcsh:Science Myofibroblasts Connective Tissue Cells Cellular Stress Responses Multidisciplinary biology Cell Differentiation respiratory system Nucleic acids Immunoblot Analysis Connective Tissue Cell Processes Gene Knockdown Techniques 030220 oncology & carcinogenesis Female Cellular Types Anatomy Myofibroblast Research Article medicine.medical_specialty animal structures Molecular Probe Techniques Research and Analysis Methods Collagen Type I Cell Line Transforming Growth Factor beta1 Bleomycin 03 medical and health sciences Heat shock protein Genetics medicine Animals Humans Non-coding RNA Molecular Biology Techniques Molecular Biology Aged lcsh:R Biology and Life Sciences Proteins Epithelial Cells Cell Biology Fibroblasts medicine.disease Actins Idiopathic Pulmonary Fibrosis Gene regulation Fibronectins Fibronectin Biological Tissue 030104 developmental biology biology.protein Cancer research RNA lcsh:Q Gene expression Collagens Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 2, p e0148998 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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