Kidney Week

Abstract: FR-PO1221

PM2.5 Induces Epithelial-to-Mesenchymal Transition by Oxidative Stress in Renal Tubular Kidney Cells

Session Information

• CKD: Mechanisms - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Kang, Duk-Hee, Ewha Womans University College of Medicine, Seoul, Korea (the Republic of)

Duk-Hee Kang, MD, PhD

• Jo, Chor ho, Ewha Womans University College of Medicine, Seoul, Korea (the Republic of)

Chor ho Jo, PhD

• Kim, Dal-Ah, Ewha Womans University College of Medicine, Seoul, Korea (the Republic of)

Dal-Ah Kim, PhD

Background

The incidence and prevalence of chronic kidney disease (CKD) are increasing worldwide. Recently, the exposure to air pollution, especially particulate matter_2.5 (PM_2.5) was newly identified to be a potential risk factor for CKD, however there are no studies on whether exposure to PM_2.5 is a direct cause of CKD ccurrence and exacerbation. Epithelial-to-mesenchymal transition (EMT) of tubular cells is one of the early mechanisms of progression of renal disease. Therefore, the identification of association between fine dust and EMT may allow to reveal the casualty toward CKD.

Methods

Fine dust collected by PM_2.5 filter (Ulaanbaatar, Mongolia) was dissolved in DMSO by sonication. Renal tubular kidney cells (NRK) were treated with dissolved PM_2.5 (2 & 5 μL/mL). EMT was evaluated by morphological changes of NRK cells and the expressions of E-cadherin, α-SMA, and vimentin after the stimulation with PM_2.5 and TGF-β (5 ng/mL) by WB and immunostaining. ROS generation was assessed by DCF-DA and MitoSox staining. RNA-seq analysis (Ebiogen, Korea) was performed to investigate which upregulated/downregulated-genes are associated with PM_2.5-induced phenotype transition in NRK cells.

Results

PM_2.5 at the concentrations of 2 and 5 μL/mL did not alter LDH release and cell proliferation up to 48 hours of exposure. PM_2.5 induced EMT of NRK cells assessed by morphologic changes associated with a decreased E-cadherin expression and de-novo expression of α-SMA and vimentin. PM_2.5 also increased DCF-DA and Mito-Sox staining. RNA-seq analysis demonstrated the differences in gene expression related to EMT (16.7%), adipokine (15.9%), apoptotic process (13.7%), and oxidative stress (12.8%). Among them, lipocalin 2 (LCN2), Interleukin-11 (IL-11), and hyaluronan synthase 2 (HAS2) expression showed the highest fold difference (2.7-folds, 2.5-folds, and 2.0-folds, respectively) between control and PM_2.5-treated NRK cells.

Conclusion

This data suggest that exposure to PM_2.5 induces EMT and oxidative stress in NRK cells, which may be one of the possible mechanisms for the association between fine dust exposure and the development of renal disease.

Funding

• Government Support – Non-U.S.