Uridine-5′-Triphosphate Partially Blocks Differentiation Signals and Favors a more Repair State in Cultured rat Schwann Cells

Abstract

Schwann cells (SCs) play a key role in peripheral nerve regeneration. After damage, they respond acquiring a repair phenotype that allows them to proliferate, migrate and redirect axonal growth. Previous studies have shown that Uridine-5′-Triphosphate (UTP) and its purinergic receptors participate in several pathophysiological responses in the nervous system. Our group has previously described how UTP induces the migration of a Schwannoma cell line and promotes wound healing. These data suggest that UTP participates in the signaling involved in the regeneration process. In the present study we evaluated UTP effects in isolated rat SCs and cocultures of SCs and dorsal root ganglia neurons. UTP reduced cAMP-dependent Krox-20 induction in SCs. UTP also reduced the N-cadherin re-expression that occurs when SCs and axons make contact. In myelinating cocultures, a non-significant tendency to a lower expression of P0 and MAG proteins in presence of UTP was observed. We also demonstrated that UTP induced SC migration without affecting cell proliferation. Interestingly, UTP was found to block neuregulin-induced phosphorylation of the ErbB3 receptor, a pathway involved in the regeneration process. These results indicate that UTP could acts as a brake to the differentiation signals, promoting a more migratory state in the repair-SCs.