RRC ID 63439
Author Park AM, Kanai K, Itoh T, Sato T, Tsukui T, Inagaki Y, Selman M, Matsushima K, Yoshie O.
Title Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis.
Journal PLoS One
Abstract 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.
Volume 11(2)
Pages e0148998
Published 2016-1-1
DOI 10.1371/journal.pone.0148998
PII PONE-D-15-36446
PMID 26859835
PMC PMC4747463
MeSH Actins / physiology Aged Animals Bleomycin / pharmacology* Cell Differentiation / drug effects Cell Differentiation / physiology* Cell Line Collagen Type I / physiology Female Fibroblasts / drug effects Fibroblasts / physiology Fibronectins / physiology Gene Knockdown Techniques HSP27 Heat-Shock Proteins / physiology* Humans Idiopathic Pulmonary Fibrosis / physiopathology Male Mice Myofibroblasts / physiology* Osteopontin / physiology Polymerase Chain Reaction Pulmonary Fibrosis / chemically induced* Pulmonary Fibrosis / physiopathology Transforming Growth Factor beta1 / physiology
IF 2.74
Human and Animal Cells MRC-5(RCB0218)