Cellular localization of gene expression for progranulin

Granulins, also called epithelins, are 6-kD peptides with growth modulatory effects on a variety of cells. The granulin/epithelin precursor supports t umorigenesis in appropriate cell models and is the only growth factor able to overcome the cell cycle block that occurs in murine fibroblasts after de letion of a functional IGF-1 receptor. However, little is known of the role of granulin/epithelin gene products in vivo. To understand the physiologic al role of granulins it is essential to know the cell types and conditions in which it is expressed. We examined granulin/epithelin gene expression in adult rodents by in situ hybridization. The granulin/epithelin precursor i s constitutively expressed in a number of epithelia, particularly in the sk in, GI tract, and reproductive system. Other epithelia express the gene les s strongly. Progranulin is expressed in immune cells in vivo and in specifi c neurons in the brain, including Purkinje cells, pyramidal cells of the hi ppocampus, and some cerebral cortical neurons. Little expression was detect ed in muscle cell, connective tissue, or endothelium. Cumulatively, these r esults define the basal gene expression of a new growth factor system a nd suggest that the progranulin/epithelin gene is multifunctional, with import ant constitutive roles in epithelial homeostasis, reproductive, immunologic al, and neuronal function.