α6 and β1 Integrin Heterodimer Mediates Schwann Cell Interactions with Axons and Facilitates Axonal Regeneration after Peripheral Nerve Injury

Abstract

Several isoforms of integrin subunits are expressed in Schwann cells and mediate Schwann cell interactions with axons. Here, we identify α6 and β1 integrins as heterodimeric proteins expressed in Schwann cells and define their functions in axonal regeneration. α6 and β1 integrins are induced in Schwann cells in the sciatic nerve after a crush injury, and the blocking of integrin activity by siRNA expression and by treatment with anti-integrin antibodies attenuates Schwann cell contact with cultured neurons and decreases neurite outgrowth. After nerve transection, the levels of α6 and β1 integrins in the distal nerve stump are lower than those in the corresponding nerve area after a crush injury. Schwann cells prepared from the distal nerves 7 days after transection are less supportive of neurite outgrowth in co-cultured neurons than those prepared from the nerves 7 days after a crush injury. When the transected nerves are reconnected after a delay of 1 to 2 weeks, the induced levels of α6 and β1 integrins in the reconnected distal nerves are significantly reduced compared to those in the nerves after a crush injury. These changes correlate with retarded axonal regeneration in animals that have experienced nerve transections and delayed coaptation, which implies an attenuated Schwann cell capacity to support axonal regeneration due to delayed Schwann cell contact with axons. The present data suggest that α6 and β1 integrins induced in Schwann cells after nerve injury may play a role in mediating Schwann cell interactions with axons and promote axonal regeneration.

Keywords: Schwann cell; Schwann cell-axon interaction; axonal regeneration; delayed nerve regeneration; integrin; transection and coaptation.