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| Status |
Public on Apr 17, 2020 |
| Title |
Transcriptome analysis of isolated glomeruli from obese type 2 diabetic mice treated with enarodustat |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
We found that 18-week administration of a prolyl hydroxylase inhibitor, enarodustat, improved glucose/lipid metabolism of BTBR ob/ob mice, which is a model of obesity and type 2 diabetes mellitus. Enarodustat-treated mice also exhibited reduced albuminuria along with ameliorated glomerular epithelial and endothelial damage. In order to elucidate the mechanism of renoprotection, we performed microarray gene expression analysis of isolated glomeruli. The initial screening process revealed 8965 probes whose absolute values of log2 (BTBR ob/ob mice treated with enarodustat/BTBR ob/ob mice treated with vehicle-only) exceeded 0.5. We then compared the expression levels of those 8965 probes between BTBR ob/ob and wild-type mice to identify molecules that were likely to be involved in the pathogenesis of glomerular injury. Such analysis revealed 71 genes which were significantly up-regulated and 47 genes which were significantly down-regulated in BTBR ob/ob mice compared to wild-type mice. The genes were ranked according to their fold-change values, and the analysis presented Ccl2/Mcp1 as the second-most up-regulated gene in BTBR ob/ob mice. The expression level of Ccl2/Mcp1 increased by 24.42-fold in BTBR ob/ob compared to wild-type mice, and its expression in enarodustat-treated BTBR ob/ob mice was decreased to 0.62 of the vehicle-only treated BTBR ob/ob mice. Urinary CCL2/MCP-1 was indeed decreased in enarodustat-treated BTBR ob/ob mice. In vitro experiments also showed that enarodustat suppressed palmitate-induced CCL2/MCP-1 production in murine mesangial cells. Taken together, enarodustat is likely to confer renoprotection through regulating the expression of CCL2/MCP-1 in the glomerulus.
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| Overall design |
Glomeruli were isolated from three groups of mice; BTBR wild type and BTBR ob/ob mice treated with vehicle-only, and BTBR ob/ob mice treated with enarodustat. n = 3 for each group.
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| Contributor(s) |
Tanaka S, Tanaka T, Saito H, Ishimoto Y, Wakashima T, Ueda M, Fukui K, Shimizu A, Inagi R, Yamauchi T, Kadowaki T, Nangaku M |
| Citation(s) |
31996409 |
| Submission date |
May 15, 2019 |
| Last update date |
Apr 17, 2020 |
| Contact name |
Mai Sugahara |
| E-mail(s) |
sugahara-tky@umin.ac.jp
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| Organization name |
The University of Tokyo Graduate School of Medicine
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| Department |
Nephrology and Endocrinology
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| Street address |
7-3-1 Hongo
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| City |
Bunkyo-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
113-8655 |
| Country |
Japan |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA543093 |
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