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.
Highlights
Olfactory receptors (ORs), belonging to a super-family of G protein-coupled receptors, are well-recognized for their role in odor-sensation in the olfactory epithelium[1]
In order to investigate the underlying molecular mechanisms activated during the progression of chronic kidney disease (CKD), two time-course microarray datasets, GSE3649628 and GSE9657129 were reanalyzed
In order to acquire a holistic view of molecular mechanisms of kidney fibrosis, two time-course microarray datasets were reanalyzed
Summary
Olfactory receptors (ORs), belonging to a super-family of G protein-coupled receptors, are well-recognized for their role in odor-sensation in the olfactory epithelium[1]. This family of receptors was first discovered by Linda Buck and Richard Axel[1], leading to a Nobel prize in 20042. Identification of the role of these receptors in other parts of the body, such as skin[8,9], gastrointestinal[10,11,12], and the immune system[13,14] highlights the importance of further investigations on their function in the body
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
