Systems and classical biology approaches unraveled role of olfactory receptors in progression of kidney fibrosis

Abstract

The olfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are distributed 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. Transcriptional analysis demonstrated considerable changes in the expression pattern of Olfr433, Olfr129, Olfr1393, and Olfr161 during the progression of kidney fibrosis. In conclusion, our results highlight the impact of systems biology in determination of the underlying mechanisms of chronic diseases and indicate the importance of time-course approaches to unravel the patterns of gene expression. The novel ORs proposed in this study could be the subject of further functional investigations in the kidney.