Identification of tranilast-binding protein as 36-kDa microfibril-associated glycoprotein by drug affinity chromatography, and its localization in human skin.
To elucidate the molecular mechanism involved in the suppression of keloids and hypertrophic scars by tranilast, we investigated the target protein of tranilast in bovine skin and aorta. A specific tranilast-binding protein was isolated from both tissues by drug affinity chromatography and was identified as 36-kDa microfibril-associated glycoprotein (36-kDa MAGP). Binding of 36-kDa MAGP to tranilast seemed to be specific since 36-kDa MAGP could be eluted from the drug affinity column by tranilast itself and also binding of 36-kDa MAGP to other anti-allergy drugs (amlexanox and cromolyn) is significantly weaker than that to tranilast. Light and electron microscopic immunohistochemistry detected the protein at the periphery of elastic fibers in normal human skin. In hypertrophic scar tissue, however, 36-kDa MAGP was located on small bundles of microfibrils. These findings provide support for the concept that elastogenesis occurs in scar tissue and 36-kDa MAGP might be one of the targets for tranilast.
Furuichi
H
H
Department of Chemistry, Kagawa Medical University, Kagawa, 761-0793, Japan.
Yamashita
K
K
Okada
M
M
Toyoshima
T
T
Hata
Y
Y
Suzuki
S
S
Itano
T
T
Shishibori
T
T
Tokumitsu
H
H
Kobayashi
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D003285:Contractile Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003285:Contractile Proteins; D006023:Glycoproteins; C120974:MAGP-36 protein, human; D010446:Peptide Fragments; D062367:ortho-Aminobenzoates; C012293:tranilast