Abstract
We have shown that hyaluronic acid stimulates the proliferation of quiescent NIH 3T3 cells. We have shown that treatment of 1 mg/ml hyaluronic acid results in increase of tyrosine phosphorylation of two proteins, MW 124 kDa and 60 kDa as detected by anti-tyrosine antibodies by Western blot analysis. Maximum phosphorylation occurred within 2 h after addition of 1 mg/ml hyaluronic acid. Stimulation of proliferation was also accompanied by increase in c-Myc protein, which was inhibited by amlloride, an inhibitor of Na+/H+ antiporter and EGTA and increase in the steady state level of pRb, the RB gene product. These results suggest that the intracellular signal transduction pathways that mediate the stimulatory effects of hyaluronic acid on cellular proliferation are similar to those of growth factors.
Highlights
Hyaluronic acid, an extracellular matrix glycosaminoglycan, is an linear polysaccharide containing glucuronic acid and N-acetylglucosamine as a repeating unit
We have focused on the changes in the expression of c-myc and RB and tyrosine phosphorylation
For elucidation of the signal transduction pathway that is responsible for this process, first, we observed the effect of hyaluronic acid on NIH 3T3 cell proliferation
Summary
Hyaluronic acid, an extracellular matrix glycosaminoglycan, is an linear polysaccharide containing glucuronic acid and N-acetylglucosamine as a repeating unit. Interactions between hyaluronic acid and the cell surface receptors generate a variety of biochemical signaling events including transient increase of tyrosine phosphorylation of several proteins leading to focal adhesion turnover (Hall et al, 1994) and selective expression of genes (Noble et al, 1993). These results indicate that hyaluronic acid may regulate the cell proliferation through activation of FAK-Ras pathway.
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