Spinal cord injury-induced lesional expression of the repulsive guidance molecule (RGM).
The repulsive guidance molecule (RGM) is involved in the formation of the central nervous system (CNS) during development by modulating guidance of growing axons. However, a role of RGM in CNS injury remains to be established. We studied the expression of RGM in the spinal cord of rats with spinal cord injury (SCI). After SCI, RGM+ cells accumulated in lesions and peri-lesional areas. During the first days after SCI, RGM expression was confined to neurons, ballooned neurite fibers/retraction bulbs, smooth muscle/endothelial cells, and to leucocytes infiltrating the lesion. Lesional RGM expression was frequently confined to hypertrophic beta-APP+ and RhoA+ neurites/retraction bulbs. With maturation of the lesion, we observed RGM expression by components of the developing scar tissue (cicatrix), such as fibroblastoid cells, reactive astrocytes and in addition a pronounced extracellular RGM deposition resembling neo-laminae. Frequent RGM+, RhoA+ coexpression by lesional retraction bulbs represent first preliminary evidence of RGM to exert growth inhibitory effects by the second messenger system RhoA. To date, RGM is one of the most potent axonal growth inhibitors identified and present in axonal growth impediments (i) oligodendrocytes; (ii) the plexus choroideus and (iii) components of the developing scar.
Schwab
Jan M
JM
Institute of Brain Research, Eberhard-Karls-University Tuebingen, School of Medicine, Calwer Str. 3, D-72076 Tuebingen, Germany. jschwab@zeus.bwh.harvard.edu
Conrad
Sabine
S
Monnier
Philippe P
PP
Julien
Sylvie
S
Mueller
Bernhard K
BK
Schluesener
Hermann J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D017434:Protein Structure, Tertiary; D051381:Rats; D011917:Rats, Inbred Lew; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*
D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C502259:RGM protein, rat; C483496:Rgma protein, mouse