BETA-IG-H3, A NOVEL SECRETORY PROTEIN INDUCIBLE BY TRANSFORMING GROWTH-FACTOR-BETA, IS PRESENT IN NORMAL SKIN AND PROMOTES THE ADHESION AND SPREADING OF DERMAL FIBROBLASTS IN-VITRO

We have previously identified a gene, beta ig-h3, which is highly induced in A549 cells (human lung adenocarcinoma) after growth arrest by transforming growth factor-beta. The beta ig-h3 gene encodes a 683-amino-acid secretory protein termed beta IG-H3, and treatment of several cell lines with transforming growth factor-p results in increased secretion of beta IG-H3 into cell culture supernatants. In this report, we further characterize beta IG-H3 with respect to its synthesis and function. Primary human foreskin fibroblasts grown in monolayer culture produced beta IG-H3 mRNA and secreted beta IG-H3 protein into the growth media. Treatment of these cells with transforming growth factor-beta led to an increase in beta IG-H3 mRNA and protein. Cells grown on three-dimensional scaffolds secreted beta IG-H3 into the extracellular matrix, as judged by immunostaining with anti-beta IG-H3 antibodies, beta IG-H3 was also detected in normal human skin, especially in the papillary dermis. Finally, we show that recombinant beta IG-H3 supported attachment and spreading of dermal fibroblasts, suggesting that beta IG-H3 may function as an extracellular attachment protein in skin.