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Epigenome and transcriptome study of moringa isothiocyanate in mouse kidney mesangial cells induced by high glucose, a potential model for diabetic-induced nephropathy

  • Research Article
  • Theme: Natural Products Drug Discovery in Cancer Prevention
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Abstract

Moringa isothiocyanate (MIC-1) is a bioactive constituent found abundantly in Moringa oleifera which possesses antioxidant and anti-inflammation properties. However, epigenome and transcriptome effects of MIC-1 in kidney mesangial cells challenged with high glucose (HG), a pre-condition for diabetic nephropathy (DN) remain unknown. Herein, we examined the transcriptome gene expression and epigenome DNA methylation in mouse kidney mesangial cells (MES13) using next-generation sequencing (NGS) technology. After HG treatment, epigenome and transcriptome were significantly altered. More importantly, MIC-1 exposure reversed some of the changes caused by HG. Integrative analysis of RNA-Seq data identified 20 canonical pathways showing inverse correlations between HG and MIC-1. These pathways included GNRH signaling, P2Y purigenic receptor signaling pathway, calcium signaling, LPS/IL-1-mediated inhibition of RXR function, and oxidative ethanol degradation III. In terms of alteration of DNA methylation patterns, 173 differentially methylation regions (DMRs) between the HG group and low glucose (LG) group and 149 DMRs between the MIC-1 group and the HG group were found. Several HG related DMRs could be reversed by MIC-1 treatment. Integrative analysis of RNA-Seq and Methyl-Seq data yielded a subset of genes associated with HG and MIC-1, and the gene expression changes may be driven by promoter CpG status. These genes include Col4a2, Tceal3, Ret, and Agt. In summary, our study provides novel insights related to transcriptomic and epigenomic/CpG methylomic alterations in MES13 upon challenged by HG but importantly, MIC-1 treatment reverses some of the transcriptome and epigenome/CpG methylome. These results may provide potential molecular targets and therapeutic strategies for DN.

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Abbreviations

DEGs:

Differential expressed genes

DMRs:

Differentially methylation regions

DN:

Diabetic nephropathy

DSS:

Dextran sulfate sodium

ESRD:

End-stage renal disease

HG:

High glucose

IPA:

Ingenuity Pathway Analysis

ROS:

Reactive oxygen species

TSS:

Transcription start site

LG:

Low glucose

MIC-1:

Moringa isothiocyanate

MES13:

Mesangial cells

NGS:

Next-generation sequencing

Nrf2:

Nuclear factor (erythroid-derived 2)-like 2

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Funding

This study was supported by R01AT009152 from the National Center for Complementary & Alternative Medicine (NCCAM) and R01CA200129 from the National Cancer Institute (NCI). The authors appreciate all the members of Dr. Kong’s laboratory for their invaluable support and technical assistance.

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Authors and Affiliations

  1. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA

    Shanyi Li, Wenji Li, Renyi Wu, Ran Yin, Davit Sargsyan & Ah-Ng Kong

  2. Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Wenji Li

  3. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225001, People’s Republic of China

    Wenji Li

  4. Graduate Program in Pharmaceutical Science, Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA

    Davit Sargsyan

  5. Department of Plant Biology & Pathology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, 08901, USA

    Ilya Raskin

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  1. Shanyi Li
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  2. Wenji Li
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  7. Ah-Ng Kong
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Correspondence to Ah-Ng Kong.

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Guest Editors: Ah-Ng Tony Kong and Chi Chen

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Li, S., Li, W., Wu, R. et al. Epigenome and transcriptome study of moringa isothiocyanate in mouse kidney mesangial cells induced by high glucose, a potential model for diabetic-induced nephropathy. AAPS J 22, 8 (2020). https://doi.org/10.1208/s12248-019-0393-z

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