Role of placental growth factor (plgf) in the inflammatory context resulting from nerve injury, the wallerian degeneration

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Role of placental growth factor (PLGF) in the inflammatory context resulting from nerve injury, the wallerian degeneration

Linda Chaballe*, Murielle Wouters*, Lieve Moons**, Peter Carmeliet**, Jean Schoenen*, Rachelle Franzen*

*Research Center for Cellular and Molecular Neurobiology, research unit on cephalic pain and axonal regeneration, University of Liège, Liège, Belgium

**The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, Belgium

Wallerian degeneration is an active degenerative process of the distal portions of nerve axons that are separated from the parent cell body. This phenomenon includes axonal fragmentation, myelin breakdown and debris clearance by Schwann cells and macrophages recruited from the circulation. This last step is induced by an inflammatory process due to an expression of pro-inflammatory cytokines and chemoattractant molecules by Schwann cells and later by macrophages. This cyto/chemokine network is essential to provide a favourable microenvironment to successful axonal sprouting, elongation and maturation.

Placental growth factor (PLGF) is a member of the vascular endothelial growth factor (VEGF) family. Whereas PLGF has been originally identified in the placenta, its expression has been detected in several other organs including heart, lung, thyroid gland, skeletal muscles and brain and especially when cells are activated or stressed. With the exception of its proangiogenic effect, PLGF a plusierurs effets qui pourraient l’impliquer ds la dégénérescence wallérienne / qui pourrait nous interresser ds le cadre de la dégénérescence wallérienne such as its effect on monocyte activation and attraction, its ability to increase expression of pro-inflammatory cytokines and chemokines, and its role in axonal guidance via its binding to neuropilin.

In this study, we investigated PLGF expression in normal sciatic nerve and after transection by double immunofluorescence stainings, as well as PLGF role in the post-traumatic inflammatory processes in the PNS, by comparing the wallerian degeneration events in wild-type mice versus transgenic knock-out Pgf -/- mice.

We showed an axonal PLGF expression in normal sciatic nerve, which switched to Schwann cell expression during wallerian degeneration. We also demonstrated a role of PLGF in the inflammatory process of wallerian degeneration by observing a delay in events of wallerian degeneration in Pgf -/- mice.

Works supported by a grant from the National Funds for Scientific Research, Belgium And by the “Günter Verbraekel Foundation”, Erpe-Mere, Belgium
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