title: Role of heat shock protein 27 in transforming growth factor-β-stimulated vascular endothelial growth factor release in osteoblasts.
abstract: We have previously reported that transforming growth factor-β (TGF-β) stimulates heat shock protein 27 (HSP27) induction via p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase in osteoblast-like MC3T3-E1 cells, and that the release of vascular endothelial growth factor (VEGF) is induced by TGF-β in these cells. In the present study, we investigated the effect of HSP27 knockdown on the TGF-β-stimulated VEGF release in these cells. Gene silencing using short interfering RNA against HSP27 (HSP27-siRNA) significantly suppressed the TGF-β-induced VEGF release. Immunofluorescence microscopy also revealed that HSP27-siRNA suppressed the TGF-β-stimulated VEGF induction as well as the reduction of HSP27 induction in these cells. However, the mRNA expression of VEGF stimulated by TGF-β was not reduced even in cells transfected with HSP27-siRNA. These results strongly suggest that HSP27 induction is critical for TGF-β-induced VEGF release in osteoblasts.
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kato
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamauchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Natsume
authors.forename: Chiho
authors.initials: C
authors.lastname: Minamitani
authors.forename: Jun
authors.initials: J
authors.lastname: Mizutani
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D055785:Gene Knockdown Techniques; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases