Prosaposin and its receptors are differentially expressed in the salivary glands of male and female rats

Abstract

Salivary glands produce various neurotrophins that are thought to regulate salivary function during normal and pathological conditions. Prosaposin (PSAP) is a potent neurotrophin found in several tissues and various biological fluids and may play roles in the regulation of salivary function. However, little is known about PSAP in salivary glands. As the functions of salivary glands are diverse based on age and sex, this study examines whether PSAP and its receptors, G protein-coupled receptor 37 (GPR37) and GPR37L1, are expressed in the salivary glands of rats and whether sex and aging affect their expression. Immunohistochemical analysis revealed that PSAP and its receptors were expressed in the major salivary glands of rats, although their expression varied considerably based on the type of gland, acinar cells, age and sex. In fact, PSAP, GPR37 and GPR37L1 were predominantly expressed in granular convoluted tubule cells of the submandibular gland and the intensity of their immunoreactivity was higher in young adult female rats than age-matched male rats, which was more prominent at older ages (mature adult to menopause). On the other hand, weak PSAP, GPR37 and GPR37L1 immunoreactivity was observed mainly in the basal layer of mucous cells of the sublingual gland. Triple label immunofluorescence analysis revealed that PSAP, GPR37 and GPR37L1 were co-localized in the basal layer of acinar and ductal cells in the major salivary glands. The present findings indicate that PSAP and its receptors, GPR37 and GPR37L1, are expressed in the major salivary glands of rats and their immunoreactivities differ considerably with age and sex.

Salivary proteomic profile of young healthy subjects

“…Although Psap is mainly localized in lysosomes, it can also be secreted, and it has been found in several fluids including serum ( Hineno et al, 1991 ). Psap is expressed in salivary glands and its levels differ based on the type of gland, acinar cells, age, and sex ( Islam et al, 2018 ). It has been demonstrated that Psap −/− mice develop inflammation, plaque formation and show a reduction of oxidative phosphorylation thus pointing out Psap as a potential therapeutic target for atherosclerosis ( van Leent et al, 2021 ).…”

Orphan G Protein-Coupled Receptor GPR37 as an Emerging Therapeutic Target

“…Another suspected peptide ligand with an EC 50 of 7.0 nM for GPR37 is prosaposin (PSAP), a multifunctional protein precursor to saposin A–D, that internally regulates lysosomal enzyme function and externally acts as a neuroprotective and glio-protective secretory factor. ,, It has been found that extracellular PSAP is necessary for the partitioning of GM1 ganglioside-containing lipid rafts in the plasma membrane of live cells expressing turbo green fluorescent protein-tagged (tGFP) GPR37 . Lipid rafts are specialized structures on the plasma membrane enriched in cholesterol, certain gangliosides, and lipids, and these membrane domains can coordinate the signaling of membrane receptors, including GPCRs .…”