GSE65193
The activation of the NF-?B-JNK pathway is independent of the PI3K-Rac1-JNK pathway involved in the bFGF-regulated human fibroblast cell migration
Wound healing is a complex process that repairs organ-tissues including skin after injury. Cell migration is an important process of wound healing and fibroblast growth factor bFGF has been reported to accelerate cell migration. However, knowledge of how bFGF regulates cell migration is limited. Here, we used human foreskin fibroblast primary cells and RNA-Seq based transcriptome analysis to isolate bFGF-regulating signal pathways that regulate cell migration. Among the many pathways identified, an inflammatory response pathway was further examined for its role in fibroblast cell migration through analysis of function by the key regulator NF-?B. Application of Bay11-7082 and LPS, a typical inhibitor and inducer of inflammatory response, promoted and inhibited cell migration, respectively. Biochemical data showed that Bay11-7082 treatment induces the phosphorylation level of JNK,but PI3K inhibitor LY294002 application did not alter the I?Ba phosphorylation level. In addition, Bay11-7082 and JNK inhibitor SP600125 together inhibit while LY294002 together with Bay11-7082 maintains normal cell migration, indicating that NF-?B is independent of the PI3K pathway for regulation of JNK activity during cell migration. Taken together, the present study broadens our understanding of the bFGF-regulation mechanism and further identifies a new bFGF-regulating mechanism by which NF-?B regulates JNK during human fibroblast cell migration. Overall design: In this study, we utilized a RNA-Seq approach to isolate bFGF-regulating gene pools and to further identify target molecules that regulate human fibroblast cell migration.