Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation.
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.
Akassoglou
Katerina
K
Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Yu
Wei Ming
WM
Akpinar
Pinar
P
Strickland
Sidney
S
D000818:Animals; D001369:Axons / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009186:Myelin Sheath / Q000235:genetics / Q000502:physiology*; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism*
D005353:Fibronectins; D005337:Fibrin; D005340:Fibrinogen; D020928:Mitogen-Activated Protein Kinases