Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation

Neuron. 2002 Mar 14;33(6):861-75. doi: 10.1016/s0896-6273(02)00617-7.


Remyelination is a critical step for functional nerve regeneration. Here we show that fibrin deposition in the peripheral nervous system after injury is a key regulator of remyelination. After sciatic nerve crush, fibrin is deposited and its clearance correlates with remyelination. Fibrin induces phosphorylation of ERK1/2 and production of p75 NGF low-affinity receptor in Schwann cells and maintains them in a nonmyelinating state, suppresses fibronectin production, and prevents synthesis of myelin proteins. In mice depleted of fibrin(ogen), remyelination of myelinated axons is accelerated due to the faster transition of the Schwann cells to a myelinating state. Regulation of fibrin clearance and/or deposition could be a key regulatory mechanism for Schwann differentiation after nerve damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Fibrin / metabolism*
  • Fibrinogen / metabolism
  • Fibronectins / metabolism
  • Gene Expression Regulation / physiology
  • Immunohistochemistry
  • In Situ Hybridization
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Myelin Sheath / genetics
  • Myelin Sheath / physiology*
  • Schwann Cells / cytology
  • Schwann Cells / physiology*
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism*


  • Fibronectins
  • Fibrin
  • Fibrinogen
  • Mitogen-Activated Protein Kinases