4-Methylumbelliferone inhibits hyaluronate synthesis in human uterine cervical fibroblasts.
OBJECTIVE
Hyaluronate plays an important role in the regulation of cervical function during parturition. In our previous study we showed that 4-methylumbelliferone (MU) suppresses hyaluronate synthesis by cultured human skin fibroblasts. The present study investigated the effects of MU on fibroblasts obtained from the human uterine cervix and assessed the possibility of controlling cervical ripening with MU.


METHODS
Human uterine cervical fibroblasts were collected from uterine cervices obtained from the uteri of three patients who had a total hysterectomy for uterine myoma at Hirosaki University Hospital. The fibroblasts were cultured in Dulbecco's modified Eagle's medium until confluence. They were then cultured in medium containing [3H]glucosamine (0.074 MBq/mL) with various MU doses. Hyaluronate synthesis was evaluated by assessing the incorporation of [3H]glucosamine into the soluble fraction of hyaluronate. Three independent studies were carried out on each specimen to clarify whether MU causes compositional changes or promotes hyaluronate degradation, whether the inhibitory effects of MU on hyaluronate synthesis are dose-dependent, and whether the effects of MU are reversible.


RESULTS
MU added to the medium of the cultured cells reduced the synthesis of hyaluronate in a dose-dependent manner. After MU was removed from the medium, hyaluronate synthesis recommenced, and the amount of [3H]hyaluronate synthesized was similar to the control level.


CONCLUSIONS
MU inhibits the synthesis of hyaluronate in human uterine cervical fibroblasts.
Tanaka
Kanji
K
Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, Hirosaki, Japan. kanji@cc.hirosaki-u.ac.jp
Taniguchi
Ryousuke
R
Higuchi
Tsuyoshi
T
Ozaki
Takashi
T
Mizunuma
Hideki
H
Takagaki
Keiichi
K
D002478:Cells, Cultured; D002584:Cervix Uteri / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000494:pharmacology
D006923:Hymecromone; D006820:Hyaluronic Acid