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Abstract: SA-PO401

Effects of Electronic Cigarette Aerosol Exposure on Kidney Health in Diabetic/Obese Mice

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Authors

  • Raja, Amna, New York University Grossman School of Medicine, New York, New York, United States
  • Chhaya, Dweet Gaurang, New York University Grossman School of Medicine, New York, New York, United States
  • Veerappan, Arul, New York University Grossman School of Medicine, New York, New York, United States
  • Awada, Christina, New York University Grossman School of Medicine, New York, New York, United States
  • Seshan, Surya V., Weill Cornell 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

Diabetes is one of the most important risk factor for chronic kidney disease (CKD) and end stage kidney disease. Tobacco smoking accelerates the progression of CKD of different etiologies including diabetes. However, whether e-cig use also has a deleterious effect on CKD progression is unknown. The aim of this study was to examine whether inhalation exposure of diabetic adult mice to e-cig aerosols, with and without nicotine, changes gene expression linked to kidney injury.

Methods

7-8-wk-old BTBR obese mice, a model of type II diabetes, were exposed to: 1) filtered air (control); 2) Propylene glycol/ Vegetable glycerin PG/VG (1:1); or 3) PGVG (1:1) + Nicotine (36 mg/ml) for 10-wk (3hr/d; /5d/wk). After euthanasia, kidneys were collected for RNAseq and histology. After RNA extraction, bulk RNAseq was performed, followed by RNAseq libraries preparation with TruSeq Stranded Total RNA kit (Illumina). Libraries were sequenced and aligned against mouse genome. Differential gene expression analysis was performed with DESeq2 R/Bioconductor package. The 2nd kidney from each mouse was fixed in formalin and used to assess kidney injury in PAS-stained slides.

Results

Inhalation exposure of mice to PG/VG + nicotine resulted in gene expression changes in 724 genes, while only 3 genes were differently expressed in the PG/VG group, compared to controls. Kidney injury related genes (i.e., Rorc, Col4a3, EGFR, LRRK2, VDR), cancer related genes (e.g., Adamts1, Ccn1, Ackr3) and immune-regulatory (e.g., Ace2, Rorc, Cxcl6, Ccn1), were upregulated in the PG/VG + nicotine exposed group compared to controls. In the PG/VG only group, pro-inflammatory (Rorc) was upregulated, while inflammation-protective Nr1d and kidney injury-associated Mt1 genes were downregulated. Kidney histology showed mesangial expansion consistent with diabetic nephropathy, which was similar in all 3 exposure groups.

Conclusion

Long-term, repeated exposure of diabetic mice to e-cig aerosols containing nicotine induces significant changes in genes involved in CKD progression, cancer, and inflammation. This groundbreaking study reveals 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

  • NIDDK Support