Effect of a hyaluronan synthesis inhibitor, 4-methylumbelliferone (4MU), on a stromal endometrial cell line.

OLIVARES C; CHIAPPINI F; IBAÑEZ PADILLA MC; RANDI A; MERESMAN G; MC CORMACK B; BARAÑAO RI

Congreso; LXIII Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), LXVI Sociedad Argentina de Inmunología (SAI) y Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2018

HA-CD44 interaction has been described in physiologic and pathologic conditions. Adherence, migration, invasion, proliferation and angiogenesis are amongst the processes they promote.Endometriosis is a benign disease that relies on these processes and is characterized by the presence of endometrial tissue outside the uterine cavity. It is mostly accepted that the tissue reaches this ectopic site through retrograde menstruation, causing in many cases, pain and infertility.Hyaluronic Acid (HA) is the main component of the extracellular matrix. It is a disaccharide composed of D-glucuronic acid and N-acetyl glucosamine. Its molecular weight can vary from 105 to 107 Da. There are three enzymes responsible of its synthesis: hyaluronic acid synthase (HAS)-1, -2 and -3; and four hyaluronidases (Hyal-1, -2, -3 and -4) which are responsible of its degradation.HA-synthesis inhibition, is achievable using 4-methylumbelliferone (4MU). Its mechanism of action consists on depleting the cell from UDP-glucuronic acid and downregulating HAS-2 and -3.The aim of the present study was to evaluate the effect of 4MU on cell proliferation, wound healing and gelatinase activity of an human endometrial stromal cell line.Cell proliferation of T-HESC was significantly inhibited by 1, 2 and 4 mM 4MU. Even at 0.5 mM 4MU, the migration of the cells was significantly inhibited and the scratch was closed in a low percentage. Preliminary results of MMP-2 and MMP-9 activities revealed that these gelatinases would not be modulated after 4MU treatment, but the n should be increased.More studies are needed to understand the implication of hyaluronan synthesis inhibition on the migratory capacity of the cells and which molecules are involved in this matter. Nevertheless, given our background on targeting hyaluronan on endometriosis models we are encouraged to continue investigating on this path.