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Kidney Week

Abstract: PO0625

A Comprehensive Transcriptome Profiling of Adipocyte Na-K-ATPase Signaling in Uremic Cardiomyopathy by RNA Sequencing Analysis

Session Information

  • CKD Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Author

  • Sodhi, Komal, Joan C Edwards School of Medicine at Marshall University, Huntington, West Virginia, United States
Background

Oxidant stress plays a key role in the development and progression of uremic cardiomyopathy. We have recently demonstrated that adipocyte dysfunction and uremic cardiomyopathy developed in partial nephrectomy mice model, were significantly ameliorated by adipocyte-specific expression of NaKtide, an antagonist of Na/K-ATPase signaling. Hence, to better characterize the cellular transcriptome that are involved in various biological pathways associated with adipocyte function, we aim to explore the genomic approach in the present study, through RNAseq analysis.

Methods

For invitro studies, mouse adipocytes were subjected to oxidized LDL (oxLDL) or indoxyl sulfate (IS) with or without pNaKtide treatments. Partial nephrectomy was performed in C57Bl6 mice in order to produce experimental uremic cardiomyopathy. Specific expression of NaKtide in adipocytes was achieved using a lentivirus construct driven by an adiponectin promoter. A complete RNAseq analysis was performed using DESeq2 R package in combination with packages to perform over-representation analysis (ORA) and gene set enrichment analysis (GSEA).

Results

Several gene subsets corresponding to various biological processes and molecular phenotype were differentially expressed in adipocytes with in vitro oxLDL/IS treatments and in vivo PNx model. These genes, compared using GSEA analysis, showed that more than 75% of the Kegg pathways were similar among the in vitro treatments and in vivo model. The pathways that were common between in vitro and in vivo treatments, including adipogenesis, ROS signaling, inflammatory response and oxidative phosphorylation pathways, have profound impact on the pathogenesis of uremic cardiomyopathy. The overall analysis showed a widespread normalization of gene expression by pNaKtide/adipose specific NaKtide treatments that were altered in uremic cardiomyopathy.

Conclusion

The study provides a detailed genome-wide molecular information about adipocyte function in relation to uremic cardiomyopathy pathogenesis. These data provide deeper insight into the activation of pathways associated with adipocyte Na/K-ATPase signaling, which may be a viable clinical target for the prevention and treatment of uremic cardiomyopathy.

Funding

  • Private Foundation Support