Involvement of intracellular expression of FGF12 in radiation-induced apoptosis in mast cells.
Several fibroblast growth factors (FGFs) are able to reduce and improve radiation-induced tissue damage through the activation of surface fibroblast growth factor receptors (FGFRs). In contrast, some FGFs lack classical signal sequences, which play roles in the release of FGFs, and the intracellular function of these FGFs is not well clarified. In this study, we evaluated the transcript levels of 22 FGFs in a human mast cell line, HMC-1, using quantitative RT-PCR and found that FGF2 and FGF12 were expressed in HMC-1 cells. FGF12 not only lacks classical signal sequences but also fails to activate FGFRs. HMC-1 cells were transfected with an expression vector of FGF12 to clarify the intracellular function of FGF12 after irradiation. The overexpression of FGF12 in HMC-1 cells decreased ionizing radiation-induced apoptosis, and siRNA-mediated repression of FGF12 expression augmented apoptosis in HMC-1 cells. The overexpression of FGF12 strongly suppressed the marked augmentation of apoptosis induced by inhibition of the MEK/ERK pathway with PD98059. In contrast, the mitogen-activated protein kinase (MAPK) scaffold protein islet brain 2 (IB2), which was reported to bind to FGF12, did not interfere with the anti-apoptotic effect of FGF12. The expression of FGF12 transcripts was also detected in murine cultured mast cells derived from bone marrow or fetal skin. These findings suggest that FGF12 intracellularly suppresses radiation-induced apoptosis in mast cells independently of IB2.
Nakayama
Fumiaki
F
Bundeswehr Institute of Radiobiology, Neuherbergstrasse 11, Munich, Germany. f_naka@nirs.go.jp
Müller
Kerstin
K
Hagiwara
Akiko
A
Ridi
Roland
R
Akashi
Makoto
M
Meineke
Viktor
V
D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D008407:Mast Cells / Q000378:metabolism* / Q000528:radiation effects*; D011829:Radiation Dosage
C486356:FGF12 protein, human; D005346:Fibroblast Growth Factors