Olfactory receptors contribute to progression of kidney fibrosis

Abstract

Olfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are shown to be expressed in several non-sensory tissues. Despite the specified role of some of these receptors in normal physiology of the kidney, little is known about their potential effect in renal disorders. In this study, using the holistic view of systems biology, it was determined that ORs are significantly changed during the progression of kidney fibrosis. For further validation, common differentially expressed ORs resulted from reanalysis of two time-course microarray datasets were selected for experimental evaluation in a validated murine model of unilateral ureteral obstruction (UUO). Transcriptional analysis by real-time quantitative polymerase chain reaction demonstrated considerable changes in the expression pattern of Olfr433, Olfr129, Olfr1393, Olfr161, and Olfr622 during the progression of kidney fibrosis. For localization of these ORs, single-cell RNA-sequencing datasets of normal and UUO mice were reanalyzed. Results showed that Olfr433 is highly expressed in macrophages in day-2 and 7 post-injury in UUO mice and not in normal subgroups. Besides, like previous findings, Olfr1393 was shown to be expressed prominently in the proximal tubular cells of the kidney. In conclusion, our combinatorial temporal approach to the underlying mechanisms of chronic kidney disease highlighted the potential role of ORs in progression of fibrosis. The expression of Olfr433 in the macrophages provides some clue about its relation to molecular mechanisms promoted in the fibrotic kidney. The proposed ORs in this study could be the subject of further functional assessments in the future.

CCL7 and olfactory transduction pathway activation play an important role in the formation of CaOx and CaP kidney stones

“…Furthermore, Pluznick et al determined that Olfr78 regulates blood pressure by interacting with byproducts of gut microbiota ( Pluznick et al, 2013 ). Moreover, a recent study by Motahharynia et al revealed that olfactory receptors contribute to the progression of kidney fibrosis ( Motahharynia et al, 2022 ).…”

Genome-wide association analysis of cystatin-C kidney function in continental Africa

“… 30 The little we know is that ORs significantly change during the progression of kidney fibrosis. 31 …”

Role of Ectopic Olfactory Receptors in the Regulation of the Cardiovascular–Kidney–Metabolic Axis

“…While the participation of renal OR signaling in the pathophysiology of kidney diseases has not yet been established, a few studies have pointed out a correlation between altered OR expression, the activation of pro-fibrotic pathways, and the development of renal fibrosis leading to CKD [108,109]. The formation of kidney stones, which is a risk factor for CKD, has also been associated with dysregulated expression of several ORs in the renal papillary tips [110,111].…”