Abstract: TH-PO1125
Effects of Long-Term Electronic-Cigarette (E-cig) Aerosol Exposure and Kidney Health in Mice
Session Information
- CKD: Mechanisms - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Raja, Amna, New York University Grossman School of Medicine, New York, New York, United States
- Poindexter, Morgan Elizabeth, University of California Davis, Davis, California, United States
- Awada, Christina, New York University Grossman School of Medicine, New York, New York, United States
- Zelikoff, Judith Terry, New York University Grossman School of Medicine, New York, New York, United States
- Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
Background
The link between nicotine/cigarette smoke and chronic kidney disease (CKD) is well-established. In contrast, the relationship between E-cigarette (e-cig) use and kidney injury, is relatively unknown. The aim of this toxicological study was to examine whether inhalation exposure of healthy adult mice to e-cig aerosols, with and without nicotine, produces gene expression changes linked to kidney injury.
Methods
7-8-week-old FVB/NJ mice were exposed to either: 1) filtered air (control); 2) PG/VG (1:1); or 3) PG/VG (1:1) + Nicotine (24 mg/ml) for 3-mo (5d/wk). RNA was extracted from the kidney and bulk RNAseq was performed, followed by RNAseq libraries preparation with TruSeq Stranded Total RNA kit (Illumina). Libraries were sequenced and aligned against the mouse genome. Differential gene expression analysis was performed with DESeq2 R/Bioconductor package. Ingenuity Pathway Analyses (IPA) was then used to comprehensively analyze the differentially expressed genes (DEGs) in order to infer the underlying causes of the observed fold-changes and predict downstream health events.
Results
Inhalation exposure of mice to PG/VG + nicotine resulted in gene expression changes in 61 genes, compared to the air control group; only 7 genes were differently expressed in the PG/VG group, compared to control. Changes in kidney injury-related genes (i.e., Adrb3, Ca4, Ca3, Lep, Mfsd2a, Adipoq, Angptl4, Cd1d) were observed in the kidneys of mice exposed to PG/VG + Nic aerosol, compared to filtered air controls. IPA analysis revealed that gene expression changes observed in PG/VG + Nic exposed mice are related to transcription regulation, adipogenesis and circadian rhythm signaling pathways. Organismal injury, nutritional disease and connective tissue disorders were the top diseases based on gene expression changes. In contrast, mice exposed to PG/VG aerosol, without nicotine demonstrated an upregulation of kidney-injury related genes (i.e., Upk2, and Myc), compared to the control group.
Conclusion
This study indicates that long-term, repeated exposure of adult male mice to e-cig aerosols alters the expression of kidney-injury related genes. This groundbreaking study and overlooked research area demonstrates the kidney as a target of e-cig use, and opens the door for further research concerning the impact of e-cig use on kidney health.
Funding
- Other NIH Support