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Integrative informatics analysis identifies that ginsenoside Re improves renal fibrosis through regulation of autophagy

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Abstract

We previously demonstrated that ginsenoside Re (G-Re) has protective effects on acute kidney injury. However, the underlying mechanism is still unclear. In this study, we conducted a meta-analysis and pathway enrichment analysis of all published transcriptome data to identify differentially expressed genes (DEGs) and pathways of G-Re treatment. We then performed in vitro studies to measure the identified autophagy and fibrosis markers in HK2 cells. In vivo studies were conducted using ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN) models to evaluate the effects of G-Re on autophagy and kidney fibrosis. Our informatics analysis identified autophagy-related pathways enriched for G-Re treatment. Treatment with G-Re in HK2 cells reduced autophagy and mRNA levels of profibrosis markers with TGF-β stimulation. In addition, induction of autophagy with PP242 neutralized the anti-fibrotic effects of G-Re. In murine models with UUO and AAN, treatment with G-Re significantly improved renal function and reduced the upregulation of autophagy and profibrotic markers. A combination of informatics analysis and biological experiments confirmed that ginsenoside Re could improve renal fibrosis and kidney function through the regulation of autophagy. These findings provide important insights into the mechanisms of G-Re’s protective effects in kidney injuries.

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Data availability

Publicly available datasets were used in this study. These can be found in GEO (https://www.ncbi.nlm.nih.gov/geo/) with accession numbers: GSE116121, GSE114040, GSE99505, GSE93356, GSE85871, GSE75570, GSE31959 and GSE17541.

Abbreviations

AAN:

Aristolochic acid nephropathy

ACR:

Albumin-to-creatinine ratio

AMPK:

AMP-activated protein kinase

BUN:

Blood urea nitrogen

CON:

Control

EMT:

Epithelial–mesenchymal transition

ERK:

Extracellular signal-regulated kinase

FBS:

Fetal bovine serum

G-Re:

Ginsenoside Re

H&E:

Hematoxylin and eosin staining

LC3:

Microtubule-associated protein 1A/1B-light chain 3

mTOR:

Mammalian target of rapamycin complex 1

PKB:

Protein kinase B

qPCR:

Quantitative polymerase chain reaction

TGF-β:

Transforming growth factor beta

UUO:

Unilateral ureter obstruction

VEGF:

Vascular endothelial growth factor

α-SMA:

α-Smooth muscle actin

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Acknowledgements

Not applicable.

Funding

This study was supported by grants (YDZJ202201ZYTS107, YDZJ202201ZYTS020) from Jilin Natural Science Foundation of the Jilin Science and Technology Department of China (Y. Liu).

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Authors and Affiliations

  1. Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, China

    Yingying Liu

  2. Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Yingying Liu, Lingyun Mou, Zhengzi Yi, Qisheng Lin, Khadija Banu, Chengguo Wei & Xiaoxia Yu

  3. Institute of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, Lanzhou, China

    Lingyun Mou

  4. Division of Nephrology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China

    Xiaoxia Yu

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  1. Yingying Liu
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  4. Qisheng Lin
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Contributions

X. Yu and C. Wei conceived and designed the experiments. Y. Liu, L. Mou and Q. Lin performed the experiments. Z. Yi, Y. Liu, L. Mou and K. Banu performed the data analysis. X. Yu and C. Wei drafted and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Chengguo Wei or Xiaoxia Yu.

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The animal study protocol was approved by the Institutional Animal Care and Use Committee at the Icahn School of Medicine at Mount Sinai (protocol code: IACUC-2014–0175).

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Liu, Y., Mou, L., Yi, Z. et al. Integrative informatics analysis identifies that ginsenoside Re improves renal fibrosis through regulation of autophagy. J Nat Med (2024). https://doi.org/10.1007/s11418-024-01800-7

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