PDGF Gene Therapy Enhances Expression of VEGF and bFGF Genes and Activates the NF-??B Gene in Signal Pathways in Ischemic Flaps

Abstract

Gene therapy is a novel approach for enhancing the viability of ischemic flaps. Expression of growth factor genes pertinent to angiogenesis and activation of genes of relevant signal pathways are imperative for improving flap viability. The authors investigated the gene expression profiles of growth factors and signal transduction pathways in ischemic flaps after PDGF gene therapy. Twenty Sprague-Dawley rats were divided into two groups. The experimental group (n = 10) received the plasmid vector containing the PDGF cDNA injected into the dermis of the flap area, whereas the control group (n = 10) received the physiologic saline. Seven days later, a dorsal random flap was raised. Seven days after surgery, flap viability was assessed, and expression of VEGF, bFGF, TGF-beta1, NF-kappaB, Erk2, Stat1, and Smad2 genes of the NF-kappaB, MAPK, JAK-STAT, and Smad pathways was assessed by quantitative analysis of the products of reverse-transcriptase polymerase chain reaction. Transfer of exogenous PDGF gene significantly improved flap viability (p = 0.011). Levels of expression of VEGF and bFGF genes in the flap were significantly elevated after PDGF gene transfer (p = 0.0001 and p = 0.001, respectively). Expression of the NF-kappaB gene was significantly elevated (p = 0.041). In contrast, expression of TGF-beta1, and Erk2, Stat1, and Smad2 genes was not changed. Transfer of exogenous PDGF gene to ischemic flaps promotes expression of VEGF and bFGF genes and activation of NF-kappaB gene in addition to its effects on the PDGF gene. The finding implies that transfer of the gene of one growth factor ultimately improves the expression of the genes of multiple growth factors. Activation of the NF-kappaB gene suggests that the NF-kappaB pathway may be important in enhancement of flap viability and will likely be a target of future efforts of regulation of signaling process in treatment of ischemic flaps.