Identification and characterization of three cDNAs that encode putative novel hyaluronan-binding proteins, including an endothelial cell-specific hyaluronan receptor

The glycosaminoglycan hyaluronan (HA) and HA-binding proteins (HABPs) serve important structural and regulatory functions during development and in ma intaining adult tissue homeostasis. Here we have identified and partially c haracterized the sequence and expression pattern of three putative novel HA BPs. DNA sequence analysis revealed that two of the novel HABPs, WF-HABP an d BM-HABP, form a unique HA-binding subfamily, whereas the third protein, O E-HABP, is more closely related to the LINK subfamily of HABPs. Northern bl otting experiments revealed that the expression of BM-HABP was highly restr icted, with substantial expression detected only in human fetal liver. In c ontrast, WF-HABP and OE-HABP mRNAs were detected in a number of tissues, wi th particularly prominent expression in highly vascularized tissues such as the heart, placenta, and lung. Additional studies showed that OE-HABP was expressed by cultured human endothelial cells, smooth muscle cells, and dif ferentiated monocytes. However, only endothelial cells expressed WF-HABP mR NA, and its expression was regulated by growth state, being most prominent in quiescent endothelial cells. We further characterized the expression of WF-HABP in in vivo and found that its expression colocalized with CD31-posi tive cells and was prominently expressed in microvessels in the human aorta and in atherectomy samples. Our data suggest that WF-HABP is an endothelia l cell-specific HA receptor and that it may serve a unique function in thes e cells. The WF-HABP gene was localized to chromosome 3p21.31 and the OE-HA BP gene to 15q25.2-25.3.