Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by adult microglia in vitro.
Spinal cord scar tissue presents a combined physical and molecular barrier to axon regeneration. Theoretically, spinal cord injuries (SCIs) can be rendered more permissive to axon growth by either suppressing synthesis of misaligned, fibrotic scar tissue and associated axon growth inhibitors, or enzymatically degrading them. We have previously shown that acute infusion of human recombinant decorin core protein into discreet stab injuries of the rat dorsal column pathways effected a major suppression of inflammation, astrogliosis, and multiple axon growth inhibitory chondroitin sulfate proteoglycans, which combined to promote rapid axon growth across the injury site. The high efficiency of chondroitin sulfate proteoglycan (CSPG) core protein suppression (approximately 90%) suggested that decorin may promote CSPG degradation in addition to suppressing CSPG synthesis. As the serine protease plasmin can degrade axon growth inhibitory CSPGs (neurocan and phosphacan) and its zymogen, plasmininogen is synthesized by microglia, we have investigated whether decorin treatment of acute SCIs and cultured adult spinal cord microglia can increase plasminogen/ plasmin synthesis. Infusion of hr-decorin over the first 8 days post-SCI induced 10- and 17-fold increases in plasminogen and plasmin protein levels, respectively, within sites of injury and a threefold increase in microglial plasminogen mRNA in vitro. In addition to potentially degrading multiple axon growth inhibitory components of the glial scar, plasmin is known to play major roles in activating neurotrophins and promoting central nervous system (CNS) plasticity. The wider implications of decorin induction of plasmin in the injured spinal cord for axon regeneration, and recovery of function at acute and chronic time points post-SCI are reviewed.
Davies
Jeannette E
JE
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Tang
Xiufeng
X
Bournat
Juan C
JC
Davies
Stephen J A
SJ
D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002921:Cicatrix / Q000473:pathology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D010958:Plasminogen / Q000096:biosynthesis*; D011509:Proteoglycans / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000378:metabolism*
C546878:DCN protein, human; D018076:DNA, Complementary; C546879:Dcn protein, mouse; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D010958:Plasminogen; D005341:Fibrinolysin