Expression of protease-activated receptor-2 during embryonic development

Abstract

Protease-activated receptor-2 (PAR-2) is the second member of a novel family of G-protein-coupled receptors, activated through proteolytic cleavage within the extracellular domain to reveal a newly formed amino terminus that acts as a tethered ligand causing receptor activation. PAR-2 is expressed in a number of adult tissues, but its distribution during development has not been characterized. Knowledge of the tissue distribution of PAR-2 during development will provide clues as to its function(s) in vivo. In the current immunohistochemical study, a polyclonal antibody raised against a peptide corresponding to the post-cleavage amino terminal sequence of PAR-2 was used to localize PAR-2 expression in developing mouse tissues. In the developing central nervous system and cardiac muscle, PAR-2 expression was detectable at embryonic day 12 and persisted throughout embryogenesis. At embryonic day 14, PAR-2 expression was strong in peripheral nerves, but either weak or absent in skin, bone, skeletal muscle, and blood vessels. In embryonic day 17 and postnatal day 1 hindlimbs, however, PAR-2 staining was observed throughout the layers of the epidermis, in osteoblasts, muscle fibers, and in vascular smooth muscle and endothelium. The pattern of PAR-2 expression observed during embryonic development and the association of expression with differentiation in certain tissues suggest compelling physiological roles for this novel receptor.