Hepatocyte growth factor induces pErk and pSTAT3 (Ser 727) to promote mitochondrial activity and neurite outgrowth in primary dorsal root ganglion cultures

Hepatocyte growth factor (HGF) promotes the neurite outgrowth of sensory neurons in developmental stages, but its role in injured peripheral nerves in adult mice remains largely been unexplored. In this study, we investigated the role of HGF in the regeneration of injured peripheral nerves using cultured dorsal root ganglions (DRGs). When cells were treated with HGF protein, the length of the neurite was increased 1.4-fold compared to the untreated control group. HGF greatly increased the level of phosphorylated STAT3 at serine 727 [pSTAT3 (Ser 727)], thereby translocating the protein to the mitochondria. HGF treatment increased the activity of mitochondrial complex I. When DRGs were cultured in the presence of U0126, a pharmacological inhibitor of Erk, the HGF-mediated increase in neurite outgrowth and the level of pSTAT3 (Ser 727) were both suppressed. Taken together, these results suggest that the HGF/c-met pathway might promote neurite outgrowth by controlling mitochondrial activity through the HGF/Erk/STAT3 axis.