Abstract
The extracellular effect of fibroblast growth factor-12 (FGF12) remains unknown because FGF12 cannot activate any fibroblast growth factor receptors (FGFRs). In contrast, we found that recombinant FGF12 was able to be internalized into the cytoplasm of the cells and identified two cell-penetrating peptide domains (CPP-M, CPP-C), which played a role in penetrating through plasma membranes. We also reported that FGF12 played an intracellular role in the inhibition of radiation-induced apoptosis and intraperitoneally added FGF12 inhibited radiation-induced apoptosis in the intestinal epithelial cells of BALB/c mice. This study evaluated the protective activity of FGF12 against radiation-induced intestinal injuries. FGF12 was administered intraperitoneally to BALB/c mice 24 h before or after total body irradiation (TBI) and the numbers of surviving crypts were determined 3.5 days after TBI with gamma-rays at 10 Gy. As a result, FGF12 significantly increased crypt survival even in the absence of heparin and FGF12-treatment significantly increased BrdU incorporation into the crypts, the depth of the crypts and the epithelial differentiation. In addition, we examined thirteen synthesized, 30-amino-acid partial peptides of the FGF12B polypeptide for their radioprotective activity using the above assays. We identified two peptides with radioprotective activity. One contained CPP-C sequence, and the other contained CPP-M sequence. These finding indicate that extracellular FGF12 strongly protects the jejunum against radiation-induced injury and suggests that cell-penetrating peptide domains are involved in this activity of FGF12.
