Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT)

Nerve injury leads to the release of a number of cytokines which have been shown to play an important role in cellular activation after peripheral ner ve injury. The members of the signal transducer and activator of transcript ion (STAT) gene family are the main mediators in the signal transduction pa thway of cytokines, After phosphorylation, STAT proteins are transported in to the nucleus and exhibit transcriptional activity. Following axotomy in r at regenerating facial and hypoglossal neurons, a transient increase of mRN A for JAK2, JAK3, STAT1, STAT3 and STAT5 was detected using in situ hybridi zation and semi-quantitative polymerase chain reaction (PCR), Of the invest igated STAT molecules, only STATE protein was significantly increased. In a ddition, activation of STAT3 by phosphorylation on position Tyr705 and enha nced nuclear translocation was found within 3 h in neurons and after 1 day in astrocytes. Unexpectedly, STAT3 tyrosine phosphorylation was obvious for more than 3 months. In contrast, none of these changes was found in respon se to axotomy of non-regenerating Clarke's nucleus neurons, although all th e investigated models express c-Jun and growth-associated protein-43 (GAP-4 3) in response to axonal injury. Increased expression of Janus kinase (JAK) and STAT molecules after peripheral nerve transection suggests changes in the responsiveness of the neurons to signalling molecules. STAT3 as a trans cription factor, which is expressed early and is activated persistently unt il the time of reinnervation, might be involved in the switch from the phys iological gene expression to an 'alternative program' activated only after peripheral nerve injury.