12 research outputs found
Increased specific binding of insulinâlike growth factorâI in healing cutaneous wounds
Insulinâlike growth factorâI is a polypeptide hormone structurally related to insulin. It is a potent mitogen that promotes growth and differentiation in many tissues. A role for insulinâlike growth factorâI in wound healing is suggested by its rapid rise in levels and increased insulinâlike growth factorâI messenger RNA expression in tissue after wounding. We designed our study to characterize possible changes in insulinâlike growth factorâI receptor binding during wound healing. Surgical wounds created on the abdominal skin of anesthetized New Zealand White rabbits were either left open or closed primarily. Sizeâ and weightâmatched specimens were harvested at wounding time (day 0), and at 1, 4, 7, 38, and 50 days after wounding. Preliminary experiments showed that the greatest difference in specific binding occurred between day 0 and day 7. 125Iâinsulinâlike growth factorâI binding studies were performed on frozen tissue specimens and autoradiography was performed and analyzed by computerized densitometry. Scatchard analysis of the binding data showed a single class of insulinâlike growth factorâI binding sites whose affinity that is, binding constant (Kd = 0.6 Ă 10â9) did not change significantly over time; in contrast there was a threefold increase in the number of receptors per milligram tissue in day 7 wound tissue versus normal skin harvested at day 0 (17.3 ± 2.6 Ă 1010 versus 4.7 ± 2.5 Ă 1010, respectively, p \u3c 0.05). Binding inhibition experiments showed that 125Iâinsulinâlike growth factorâI binding was most specific to insulinâlike growth factorâI with insulinâlike growth factorâI \u3e insulinâlike growth factorâII \u3e insulin. This increase in binding was due to upregulation of insulinâlike growth factorâI receptors rather than increased levels of insulinâlike growth factorâI binding protein as less than 20% of the threefold increase in binding at day 7 could be attributed to insulinâlike growth factorâI binding protein in membraneâfree extracts. The presence of specific, highâaffinity insulinâlike growth factorâI receptors in the skin and their upregulation at day 7 after wounding suggest that insulinâlike growth factorâI plays an important role during wound healing. Copyright © 1995, Wiley Blackwell. All rights reserve