ISCHEMIA AND REPERFUSION IMPAIR THE GENE-EXPRESSION OF ENDOGENOUS BASIC FIBROBLAST-GROWTH-FACTOR (BFGF) IN RAT SKELETAL-MUSCLES

Our previous studies showed that the amount of endogenous basic fibrob last growth factor (bFGF) was reduced after ischemia and reperfusion i nsult. One of the mechanisms involved in the decrease of endogenous bF GF is the increased destruction of this growth factor associated with oxygen free radical activation and inflammation. We hypothesized that the wounding also impairs the secretion of bFGF and examined the bFGF gene expression in skeletal muscles after ischemia and reperfusion ins ult. In this study, a rat leg ischemia (4 h) and reperfusion (24 h) in jury model was prepared and the in situ hybridization method and rever se transcriptase polymerase chain reaction technique (RT-PCR) were use d to evaluate the bFGF gene expression and its localization in control (normal) and injured rat skeletal muscles. The results showed that th e bFGF mRNA expression was localized in the cytoplasm. in control skel etal muscle, especially at the periphery inside the cells. According t o the intensity of the stain, four main classes of fibers could be ide ntified: strongly, moderately, weakly, and negatively stained fibers. Eased on the positive stain, about 82% of the total fibers examined we re positive for bFGF mRNA stain. In ischemic or ischemic and reperfuse d rat skeletal muscles, the localization of bFGF mRNA expression was s imilar to that in normal skeletal muscles, but only 52% in ischemic mu scles and 22% in ischemic and reperfused muscles had positive bFGF mRN A staining. RT-PCR confirmed a significant decrease in bFGF mRNA expre ssion in ischemic and reperfused rat skeletal muscles. These results s uggest that the acute ischemia and reperfusion not only induce the des truction of endogenous bFGF molecule, which is stored at the extracell ular matrix of the fibers, but also downregulate the bFGF gene express ion. The simultaneous dysregulation of endogenous bFGF gene expression and decreased synthesis of bFGF protein suggest a possible role of th is growth factor in delayed wound healing. (C) 1998 Academic Press.