title: Fibronectin Matrix Assembly after Spinal Cord Injury.
abstract: After spinal cord injury (SCI), a fibrotic scar forms at the injury site that is best characterized by the accumulation of perivascular fibroblasts and deposition of the extracellular matrix protein fibronectin. While fibronectin is a growth-permissive substrate for axons, the fibrotic scar is inhibitory to axon regeneration. The mechanism behind how fibronectin contributes to the inhibitory environment and how the fibronectin matrix is assembled in the fibrotic scar is unknown. By deleting fibronectin in myeloid cells, we demonstrate that fibroblasts are most likely the major source of fibronectin in the fibrotic scar. In addition, we demonstrate that fibronectin is initially present in a soluble form and is assembled into a matrix at 7 d post-SCI. Assembly of the fibronectin matrix may be mediated by the canonical fibronectin receptor, integrin α5β1, which is primarily expressed by activated macrophages/microglia in the fibrotic scar. Despite the pronounced cavitation after rat SCI, fibrotic scar also is observed in a rat SCI model, which is considered to be more similar to human pathology. Taken together, our study provides insight into the mechanism of fibrotic scar formation after spinal cord injury.
authors.affiliation: Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine , Miami, Florida.
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine , Miami, Florida.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Soderblom
authors.affiliation: Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine , Miami, Florida.
authors.forename: Michelle
authors.initials: M
authors.lastname: Trojanowsky
authors.affiliation: Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine , Miami, Florida.
authors.forename: Do-Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine , Miami, Florida.
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism; D051379:Mice; D016133:Polymerase Chain Reaction; D051381:Rats; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology*
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1
keywords: fibronectin; fibrotic scar; macrophages; microglia; spinal cord injury