Transforming growth factor beta 1-hyaluronic acid interaction.

Chick embryo skin fibroblasts release transforming growth factor beta 1 that is able to modulate glycosaminoglycan synthesis and secretion. When incubated with individual classes of glycosaminoglycans, the factor's modulatory activity was altered. To determine whether direct interactions between transforming growth factor beta 1 and glycosaminoglycans occur, we have assessed the activity of the growth factor after pre-incubation with single classes of glycosaminoglycans by assaying its inhibitory effect upon the proliferative response of thymocytes stimulated with interleukin-1. Untreated transforming growth factor beta 1 suppressed the proliferative response of thymocytes to interleukin-1, as did transforming growth factor beta 1 pre-incubated with sulphated glycosaminoglycans. By contrast, transforming growth factor beta 1 lost its inhibitory capacity when preincubated with high molecular weight hyaluronic acid. Digestion of transforming growth factor beta 1-hyaluronic acid complex with hyaluronidase released active transforming growth factor beta 1. Trypsin degraded transforming growth factor beta 1 alone, but did not degrade the transforming growth factor beta 1-hyaluronic acid complex. These results suggest that hyaluronic acid interacts with transforming growth factor beta 1, thus protecting the factor from tryptic degradation and may be a means of concentrating growth factor activity.