title: Recovery from radiation-induced bone marrow damage by HSP25 through Tie2 signaling.
abstract: OBJECTIVE
  Whole-body radiation therapy can cause severe injury to the hematopoietic system, and therefore it is necessary to identify a novel strategy for overcoming this injury.
  
  
  METHODS
  Mice were irradiated with 4.5 Gy after heat shock protein 25 (HSP25) gene transfer using an adenoviral vector. Then, peripheral blood cell counts, histopathological analysis, and Western blotting on bone marrow (BM) cells were performed. The interaction of HSP25 with Tie2 was investigated with mouse OP9 and human BM-derived mesenchymal stem cells to determine the mechanism of HSP25 in the hematopoietic system.
  
  
  RESULTS
  HSP25 transfer increased BM regeneration and reduced apoptosis following whole-body exposure to ionizing radiation (IR). The decrease in Tie2 protein expression that followed irradiation of the BM was blocked by HSP25 transfer, and Tie2-positive cells were more abundant among the BM cells of HSP25-transferred mice, even after IR exposure. Following systemic RNA interference of Tie2 before IR, HSP25-mediated radioprotective effects were partially blocked in both mice and cell line systems. Stability of Tie2 was increased by HSP25, a response mediated by the interaction of HSP25 with Tie2. IR-induced tyrosine phosphorylation of Tie2 was augmented by HSP25 overexpression; downstream events in the Tie2 signaling pathway, including phosphorylation of AKT and EKR1/2, were also activated.
  
  
  CONCLUSIONS
  HSP25 protects against radiation-induced BM damage by interacting with and stabilizing Tie2. This may be a novel strategy for HSP25-mediated radioprotection in BM.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Hae-June
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hee-Chung
authors.initials: HC
authors.lastname: Kwon
authors.forename: Hee-Yong
authors.initials: HY
authors.lastname: Chung
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001853:Bone Marrow / Q000502:physiology / Q000528:radiation effects*; D003114:Colony-Forming Units Assay / Q000379:methods; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006360:Heat-Shock Proteins; D006801:Humans; D020287:In Situ Nick-End Labeling; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones; D010766:Phosphorylation; D034622:RNA Interference; D011833:Radiation Injuries, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D042787:Receptor, TIE-2; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse