βIG-H3, a novel secretory protein inducible by transforming growth factor-β, is present in normal skin and promotes the adhesion and spreading of dermal fibroblasts in vitro

Abstract

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