Damage-Induced Neuronal Endopeptidase (DINE/ECEL) Expression Is Regulated by Leukemia Inhibitory Factor and Deprivation of Nerve Growth Factor in Rat Sensory Ganglia after Nerve Injury

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Abstract
Damage-induced neuronal endopeptidase (DINE) is a novel metallopeptidase and is expressed in response to various neuronal injuries. The expression regulation of DINE mRNA in the dorsal root ganglia (DRGs) after sciatic nerve injury is examined. A substantial increase of DINE mRNA expression was observed in relatively small-sized DRG neurons after nerve injury. The expression was observed in isolectin B4-negative and partly TrkA-positive neurons, and the expression profile was fairly similar to that of the neuropeptide galanin. More than 80% of DINE mRNA-positive neurons simultaneously demonstrated galanin immunoreactivity after nerve injury. In cultured DRG, DINE mRNA expression was enhanced by leukemia inhibitory factor (LIF) but not by other growth factors and cytokines. LIF treatment to rat sciatic nerve induced DINE mRNA expression in DRG without nerve injury, and, conversely, the intranerve injection of anti-gp130 antibody after sciatic nerve injury significantly inhibited the upregulation of DINE mRNA in DRG. Furthermore, nerve growth factor (NGF) deprivation, which can induce galanin expression, also enhanced DINE mRNA expression in vitro and in vivo. Both LIF application and NGF deprivation additively enhanced DINE expression in vitro. These results suggest that DINE gene expression is regulated separately by both LIF and NGF deprivation, and this regulation pattern is similar to that of galanin gene expression. Because both DINE and galanin have a neuroprotective function, their simultaneous induction may provide more successful protection for injured sensory neurons.