Lp3/Hapln3, a novel link protein that co-localizes with versican and is coordinately up-regulated by platelet-derived growth factor in arterial smooth muscle cells.
Link proteins (LPs) belong to the link-module superfamily, which can stabilize and enhance the binding of lecticans to hyaluronan. We report here the identification and characterization of a novel rat link protein gene (Lp3/Hapln3). The deduced protein sequence shares the typical modular elements of link proteins and has an estimated mass of 39 kDa. Examination of the rat genomic DNA sequence revealed that Lp3/Hapln3 and aggrecan genes were paired on chromosome 1q31. Another LP gene and the lectican gene were also paired at a different locus, as they are in the human and mouse genomes. Immunohistochemical analysis showed the prominent expression of Lp3/Hapln3 in the smooth muscle tissues of the vascular wall and gastrointestinal tract. Further comparative studies revealed that Lp3/Hapln3 was well co-localized with versican around the smooth muscle cells of blood vessels but not around endothelial cells. In vitro experiments using primary cultured rat arterial smooth muscle cells (ASMCs) demonstrated the coordinated up-regulation of Lp3/Hapln3 and versican by platelet-derived growth factor (PDGF). These data were supported by in vivo studies of a mechanical vascular injury model in mice. Altogether, our results suggest that Lp3/Hapln3 is involved, together with versican and hyaluronan, in the formation of the pericellular matrix of vascular smooth muscle cells.
Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Hiroko
H
Ogawa
Toshitaka
T
Oohashi
Masataka
M
Sata
Yoko
Y
Bekku
Satoshi
S
Hirohata
Keigo
K
Nakamura
Tomoko
T
Yonezawa
Shozo
S
Kusachi
Yasushi
Y
Shiratori
Yoshifumi
Y
Ninomiya
D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000302:isolation & purification; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015854:Up-Regulation; D053675:Versicans; D000099249:Proteoglycan Link Protein
D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D018076:DNA, Complementary; D006820:Hyaluronic Acid; D037181:Lectins, C-Type; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D053675:Versicans; C499787:Hapln3 protein, rat; D000099249:Proteoglycan Link Protein; C508322:VCAN protein, human; C508323:Vcan protein, mouse; C508324:Vcan protein, rat