Abstract: | The present studies demonstrate that the expression of the vitamin K-dependent matrix Gla protein (MGP) is critically dependent on cell density in culture. Subculture of confluent NRK cells to 1/30 of the confluent cell density causes a 50- to 100-fold decline in MGP expression per cell within two days. MGP expression subsequently increases with increasing cell density and eventually attains a level of expression per cell at five days post-confluence that is over 2,000-fold greater than was seen in the cells two days after the 1 to 30 subculture. These reversible, density-dependent changes in MGP expression are far larger than have been previously reported for other secreted proteins and suggest that the as yet unknown function of MGP requires its expression at high cell density but not at low. We have also observed that human epidermal growth factor (EGF) causes a 20-fold reduction in MGP expression in post-confluent, non-dividing cultures and suggest that the suppression of MGP function at high density may be a prelude to cell migration or division in response to appropriate signals. J. Cell. Physiol. 171:125–134, 1997. © 1997 Wiley-Liss, Inc. |