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 re...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-02-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-022-00217-w |
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| author | Ali Motahharynia Shiva Moein Farnoush Kiyanpour Kobra Moradzadeh Moein Yaqubi Yousof Gheisari |
| author_facet | Ali Motahharynia Shiva Moein Farnoush Kiyanpour Kobra Moradzadeh Moein Yaqubi Yousof Gheisari |
| author_sort | Ali Motahharynia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T00:00:03Z |
| format | Article |
| id | doaj.art-14d4bc8ac09040a1a9f983cc78c79e0c |
| institution | Directory Open Access Journal |
| issn | 2056-7189 |
| language | English |
| last_indexed | 2024-12-24T00:00:03Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj.art-14d4bc8ac09040a1a9f983cc78c79e0c2022-12-21T17:25:09ZengNature Portfolionpj Systems Biology and Applications2056-71892022-02-01811910.1038/s41540-022-00217-wOlfactory receptors contribute to progression of kidney fibrosisAli Motahharynia0Shiva Moein1Farnoush Kiyanpour2Kobra Moradzadeh3Moein Yaqubi4Yousof Gheisari5Regenerative Medicine Research Center, Isfahan University of Medical SciencesRegenerative Medicine Research Center, Isfahan University of Medical SciencesRegenerative Medicine Research Center, Isfahan University of Medical SciencesRegenerative Medicine Research Center, Isfahan University of Medical SciencesDepartment of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill UniversityRegenerative Medicine Research Center, Isfahan University of Medical SciencesAbstract 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.https://doi.org/10.1038/s41540-022-00217-w |
| spellingShingle | Ali Motahharynia Shiva Moein Farnoush Kiyanpour Kobra Moradzadeh Moein Yaqubi Yousof Gheisari Olfactory receptors contribute to progression of kidney fibrosis npj Systems Biology and Applications |
| title | Olfactory receptors contribute to progression of kidney fibrosis |
| title_full | Olfactory receptors contribute to progression of kidney fibrosis |
| title_fullStr | Olfactory receptors contribute to progression of kidney fibrosis |
| title_full_unstemmed | Olfactory receptors contribute to progression of kidney fibrosis |
| title_short | Olfactory receptors contribute to progression of kidney fibrosis |
| title_sort | olfactory receptors contribute to progression of kidney fibrosis |
| url | https://doi.org/10.1038/s41540-022-00217-w |
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