Tumor necrosis factor superfamily member APRIL contributes to fibrotic scar formation after spinal cord injury.
BACKGROUND
Fibrotic scar formation contributes to the axon growth-inhibitory environment that forms following spinal cord injury (SCI). We recently demonstrated that depletion of hematogenous macrophages led to a reduction in fibrotic scar formation and increased axon growth after SCI. These changes were associated with decreased TNFSF13 (a proliferation inducing ligand (APRIL)) expression, but the role of APRIL in fibrotic scar formation after SCI has not been directly investigated. Thus, the goal of this study was to determine the role of APRIL in fibrotic scar formation after SCI.


METHODS
APRIL knockout and wild-type mice received contusive SCI and were assessed for inflammatory cytokine/chemokine expression, leukocyte infiltration, fibrotic scar formation, axon growth, and cell proliferation.


RESULTS
Expression of APRIL and its receptor BCMA is increased following SCI, and genetic deletion of APRIL led to reduced fibrotic scar formation and increased axon growth. However, the fibrotic scar reduction in APRIL KO mice was not a result of changes in fibroblast or astrocyte proliferation. Rather, APRIL knockout mice displayed reduced TNFα and CCL2 expression and less macrophage and B cell infiltration at the injury site.


CONCLUSIONS
Our data indicate that APRIL contributes to fibrotic scar formation after SCI by mediating the inflammatory response.
Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL, 33136, USA.
Lucy H
LH
Funk
Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL, 33136, USA.
Amber R
AR
Hackett
Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL, 33136, USA.|Department of Cell Biology, University of Miami School of Medicine, Miami, FL, 33136, USA.|Department of Neurology, University of Miami School of Medicine, Miami, FL, 33136, USA.
Mary Bartlett
MB
Bunge
Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL, 33136, USA. JLee22@med.miami.edu.|University of Miami School of Medicine, 1095 NW 14th Terrace, LPLC 4-19, Miami, FL, 33136, USA. JLee22@med.miami.edu.
Jae K
JK
Lee
D000818:Animals; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D059467:Transcriptome; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*
C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
BAFF; BAFF-R; BCMA; Cell proliferation; Fibrosis; Glial scar; TACI; TNFSF13