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Integrated transcriptomic and proteomic analyses uncover regulatory roles of Nrf2 in the kidney.

ABSTRACT: The transcription factor Nrf2 exerts protective effects in numerous experimental models of acute kidney injury, and is a promising therapeutic target in chronic kidney disease. To provide a detailed insight into the regulatory roles of Nrf2 in the kidney, we performed integrated transcriptomic and proteomic analyses of kidney tissue from wild-type and Nrf2 knockout mice treated with the Nrf2 inducer methyl-2-cyano-3,12-dioxooleano-1,9-dien-28-oate (CDDO-Me, also known as bardoxolone methyl). After 24?h, analyses identified 2561 transcripts and 240 proteins that were differentially expressed in the kidneys of Nrf2 knockout mice, compared with those of wild-type counterparts, and 3122 transcripts and 68 proteins that were differentially expressed in wild-type mice treated with CDDO-Me, compared with those of vehicle control. In the light of their sensitivity to genetic and pharmacological modulation of renal Nrf2 activity, genes/proteins that regulate xenobiotic disposition, redox balance, the intra/extracellular transport of small molecules, and the supply of NADPH and other cellular fuels were found to be positively regulated by Nrf2 in the kidney. This was verified by qPCR, immunoblotting, pathway analysis, and immunohistochemistry. In addition, the levels of NADPH and glutathione were found to be significantly decreased in the kidneys of Nrf2 knockout mice. Thus, Nrf2 regulates genes that coordinate homeostatic processes in the kidney, highlighting its potential as a novel therapeutic target.

SUBMITTER: Shelton LM

PROVIDER: S-EPMC4676083 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Integrated transcriptomic and proteomic analyses uncover regulatory roles of Nrf2 in the kidney.

Shelton Luke M LM Lister Adam A Walsh Joanne J Jenkins Rosalind E RE Wong Michael H L MH Rowe Cliff C Ricci Emanuele E Ressel Lorenzo L Fang Yongxiang Y Demougin Philippe P Vukojevic Vanja V O'Neill Paul M PM Goldring Christopher E CE Kitteringham Neil R NR Park B Kevin BK Odermatt Alex A Copple Ian M IM

Kidney international 20150930 6

The transcription factor Nrf2 exerts protective effects in numerous experimental models of acute kidney injury, and is a promising therapeutic target in chronic kidney disease. To provide a detailed insight into the regulatory roles of Nrf2 in the kidney, we performed integrated transcriptomic and proteomic analyses of kidney tissue from wild-type and Nrf2 knockout mice treated with the Nrf2 inducer methyl-2-cyano-3,12-dioxooleano-1,9-dien-28-oate (CDDO-Me, also known as bardoxolone methyl). Aft ...[more]

PMID: 26422507

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Integrated transcriptomic and proteomic analyses uncover regulatory roles of Nrf2 in the kidney.

Publications

Integrated transcriptomic and proteomic analyses uncover regulatory roles of Nrf2 in the kidney.

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