Gl. Yao et al., SELECTIVE UP-REGULATION OF CYTOKINE RECEPTOR SUBCHAIN AND THEIR INTRACELLULAR SIGNALING MOLECULES AFTER PERIPHERAL-NERVE INJURY, European journal of neuroscience, 9(5), 1997, pp. 1047-1054
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.