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Role of the transcription factor STAT3 in Schwann cells in the processes of degeneration and regeneration in damaged nerves

Final Report Summary - STAT3-SCHWANN CELLS (Role of the transcription factor STAT3 in Schwann cells in the processes of degeneration and regeneration in damaged nerves)

Objective
The objective of the project is to establish whether STAT3 in Schwann cells is an important mediator of the adaptive injury response of these cells in damaged nerves.

Results
The results of the project show that:
• STAT3 is expressed in Schwann cells and activated after nerve injury
• STAT3 mediates survival of long-term denervated Schwann cells
• STAT3 is not required for the formation of cellular substrates for regenerating axons
• Schwann cell STAT3 does not control nerve repair

Conclusion
The preliminary data reveal that the transcription factor STAT3 in Schwann cells is not required to the formation of the Büngner bands and nerve repair but is essential for the survival of long-term denervated Schwann cells.

Objective
The objective of the project is to establish whether STAT3 in Schwann cells is an important mediator of the adaptive injury response of these cells in damaged nerves.

Results
The results of the project show that:
• STAT3 is expressed in Schwann cells and activated after nerve injury
• STAT3 mediates survival of long-term denervated Schwann cells
• STAT3 is not required for the formation of cellular substrates for regenerating axons
• Schwann cell STAT3 does not control nerve repair

Conclusion

Potencial impact
Peripheral nerve injuries are common and have a high impact on patients’ quality of life. The incidence of these injuries in Europe is 300.000 cases per year, being motor vehicle accidents, lacerations with sharp objects and long bone fractures the most common causes. Despite the avances in reparative surgical techniques, the restauration of motor and sensory functions are rarely achieve, demanding better regenerative therapies. Apart from disabling the patient, the economical load on a personal level as well as to the society is huge.

The regeneration of peripheral nerves is specially poor in humans when surgery has been delayed and/or axonal regeneration requires a long distance Due to the slow rate of neurons to regenerate (1-3mm/day), the regenerating axons remain without targets connections for months or years. Under these conditions, the Schwann cells in the distal nerve stump are chronically denervated, loosing their capacity to generate the repair cells (Büngner bands) and failing to support regenerating axons. The chronic degeneration of the distal stump leads to the death of Schwann cells and increased fibrosis, limiting the target reinnervation and recovery after delayed repair.
Our findings reveal that the tyrosine and serine phosphorylation of STAT3 is induced in the distal stump after transection of sciatic nerves. If immunohistochemical studies confirm that both STAT3 phosphorylated forms are expressed in mature and denervated Schwann cells, it will be the first study in the literature reporting the activation of STAT3 in Schwann cells in injured nerves in vivo. In addition, this study reports a role for STAT3 in Schwann cells. The preliminary data reveal that STAT3 is not required to the formation of the Büngner bands and nerve repair but is essential for the survival of long-term denervated Schwann cells. Thus, STAT3 could become a target to improve the capacity of the distal stump to support regeneration after delayed repair.