Altered expression of the MCSP/NG2 chondroitin sulfate proteoglycan in collagen VI deficiency.
NG2, the rat homologue of the human melanoma chondroitin sulfate proteoglycan (MCSP), is a ligand for collagen VI (COL6). We have examined skeletal muscles of patients affected by Ullrich scleroatonic muscular dystrophy (UCMD), an inherited syndrome caused by COL6 genes mutations. A significant decrease of NG2 immunolabeling was found in UCMD myofibers, as well as in skeletal muscle and cornea of COL6 null-mice. In UCMD muscles, truncated NG2 core protein isoforms were detected. However, real-time RT-PCR analysis revealed marked increase in NG2 mRNA content in UCMD muscle compared to controls. We hypothesize that NG2 immunohistochemical and biochemical behavior may be compromised owing to the absence of its physiological ligand. MCSP/NG2 proteoglycan may be considered an important receptor mediating COL6-sarcolemma interactions, a relationship that is disrupted by the pathogenesis of UCMD muscle.
Petrini
Stefania
S
Unit of Molecular Medicine, Bambino Gesù Hospital IRCCS, P.zza S. Onofrio 4, 00165 Rome, Italy. petrini.s@tiscalinet.it
Tessa
Alessandra
A
Stallcup
William B
WB
Sabatelli
Patrizia
P
Pescatori
Mario
M
Giusti
Betti
B
Carrozzo
Rosalba
R
Verardo
Margherita
M
Bergamin
Natascha
N
Columbaro
Marta
M
Bernardini
Camilla
C
Merlini
Luciano
L
Pepe
Guglielmina
G
Bonaldo
Paolo
P
Bertini
Enrico
E
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000172:deficiency* / Q000235:genetics; D003315:Cornea / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000503:physiopathology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D024142:Collagen Type VI; D020033:Protein Isoforms; D011509:Proteoglycans; D012333:RNA, Messenger; D000099216:Chondroitin Sulfate Proteoglycan 4