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Olfactory receptor 51E2 (OR51E2), frequently referred to by its mouse ortholog name Olfr78 or as Prostate-Specific G-Protein Coupled Receptor (PSGR), is a specialized chemosensor belonging to the G protein-coupled receptor family [1][3]. Although originally identified in the olfactory epithelium, it is notably expressed in the renal juxtaglomerular apparatus and vascular smooth muscle cells, where it senses short-chain fatty acids (SCFAs) like acetate and propionate produced by gut microbiota [1]. Activation of the receptor in the kidney triggers the release of renin, thereby playing a critical role in the regulation of systemic blood pressure and cardiovascular homeostasis [1]. Beyond its physiological role in the renal system, OR51E2 is highly overexpressed in prostate cancer, particularly in high-grade intraepithelial neoplasia and adenocarcinoma, which has led to its investigation as a diagnostic biomarker and therapeutic target [2]. In prostate cells, the receptor appears to modulate signaling pathways involved in cell proliferation and migration, often responding to ligands like beta-ionone or steroid metabolites [2][4]. Therapeutic strategies targeting OR51E2 aim to either modulate blood pressure in hypertensive patients or inhibit tumor growth in prostate cancer, though the dual functionality presents challenges for tissue-specific targeting [1][2]. Current research focuses on developing potent and selective small molecule agonists or antagonists to exploit these pathways for clinical benefit [4].
The receptor acts as a G protein-coupled receptor that, upon binding ligands such as short-chain fatty acids, activates the Gs-adenylyl cyclase-cAMP signaling pathway to stimulate renin release in the kidney or modulate cell growth in the prostate.
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