Two collagen-binding proteins, osteonectin and HSP47, are coordinately induced in transformed keratinocytes by heat and other stresses.

pSE48 was one of six clones selected by differential colony hybridization as a cDNA coding for mRNA expressed in parietal endoderm-like F9 cells and not in primitive endoderm-like F9 cells. It was sequenced and identified as a segment of mouse osteonectin (SPARC) cDNA. We found osteonectin to be heat-inducible in some cells. Expression and secretion of osteonectin were then investigated using mouse (Pam 212) and human (HSC-1) keratinocyte cell lines. Both the mRNA levels and the secretion of osteonectin increased concurrently when Pam and HSC-1 cells cultured in low calcium medium were exposed to various stresses including heat shock and treatment with sodium arsenite or L-azetidine-2-carboxylic acid. Another collagen-binding stress protein, HSP47, was also found to be expressed, synthesized, and stress-inducible in the keratinocyte cell line. The degree of HSP47 induction by various stresses was not so prominent as that of HSP70 but greater than that of osteonectin. The time courses of osteonectin and HSP47 induction by heat shock were similar to each other and distinct from HSP70; they were slower and more persistent than HSP70. We identified a heat shock element-like sequence in the promoter region of the mouse and bovine osteonectin genes. This sequence might participate in the stress induction of osteonectin. Thus, osteonectin and HSP47 share another common feature, stress-inducibility, as well as collagen-binding capacity and inducibility through differentiation, although they are quite distinct in their amino acid sequence and distribution.