SELECTIVE UP-REGULATION OF CYTOKINE RECEPTOR SUBCHAIN AND THEIR INTRACELLULAR SIGNALING MOLECULES AFTER PERIPHERAL-NERVE INJURY

Numerous studies have suggested that growth factors and cytokines play an important role in the survival of injured neurons and in neurite e longation. Therefore, intracellular signalling pathways activated by g rowth factors and cytokine receptors play an important role in neurona l survival or for the re-establishment of connection. Since the JAK (j anus kinase)-STAT (signal transducers and activators of transcription) signal transduction pathway is known to play a major role in cytokine receptor signalling, we first examined regulation of JAK gene express ion following peripheral nerve injury by in situ hybridization histoch emistry. The rat hypoglossal nerve was axotomized unilaterally and the mRNA levels for JAK1, JAK2. JAK3 and TYK2 were examined in the hypogl ossal nucleus at postoperative times ranging from 1 to 35 days. Among the JAK family members, JAK2 and JAK3 were substantially increased in injured hypoglossal motoneurons, whereas no significant increases were observed for JAK1 and TYK2. These changes were further confirmed by i mmunohistochemistry using antibodies specific to JAK2 and JAK3. In add ition, we examined the JAK2 and JAK3 associated cytokine receptor comp onents, IL-2R gamma and gp130, which are common to various cytokine re ceptors. Among these, gp130 immunostaining was upregulated after nerve injury. This was also confirmed by in situ hybridization. These resul ts suggest that the injured neuron prepares the molecular machinery in volved in certain cytokine receptor signalling pathways at an early ph ase of the regenerative process, accelerating for the neuron to respon d to cytokines that may regulate survival and/or neurite elongation.