Stimulation of small proteoglycan synthesis by the hyaluronan synthesis inhibitor 4-methylumbelliferone in human skin fibroblasts.
Human skin fibroblasts cultured with 4-methylumbelliferone (MU), a hyaluronan synthesis inhibitor, produce a hyaluronan-deficient extracellular matrix (See [9]). Our present study investigated the effects of MU on proteoglycan, which is the other main component of the extracellular matrix, and interacts with hyaluronan. Proteoglycans isolated from culture medium in the presence or absence of MU were characterized by gel-filtration chromatography, ion-exchange HPLC, electrophoresis, and immunoblotting. We found that MU had only a negligible effect on the synthesis of large proteoglycan but increased the production of small proteoglycan in comparison with cultures lacking MU. This small proteoglycan was identified by immunoblotting as decorin. The structures of decorin synthesized in the presence and absence of MU were compared by gel-filtration chromatography, and the data indicated that cells incubated with MU produced a larger decorin molecule than cells incubated without MU. Furthermore, the two decorins had galactosaminoglycan chains of different sizes. These results suggest that MU inhibits the synthesis of hyaluronan and accelerates production of the larger decorin in the extracellular matrix.
Funahashi
Masaru
M
Department of Glycotechnology, Center for Advanced Medical Research, and Departments of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Japan. seika1@cc.hirosaki-u.ac.jp
Nakamura
Toshiya
T
Kakizaki
Ikuko
I
Mizunuma
Hideki
H
Endo
Masahiko
M
D002478:Cells, Cultured; D058575:Decorin; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000302:isolation & purification; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D006923:Hymecromone; D006820:Hyaluronic Acid