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Abstract: FR-PO092

Stress Granule Plays a Protective Role in Renal Proximal Tubular Cells

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Wang, Shixuan, Medical College of Georgia, Augusta, Georgia, United States
  • Dong, Zheng, Medical College of Georgia, Augusta, Georgia, United States
Background

Stress granule (SG) is one type of cytoplasmic structures formed in eukaryotic cells upon certain types of stress. Further study disclosed that SG mainly contains RNA-binding proteins (RBPs) and mRNAs. SGs are widely regarded as one mechanism for cells to survive a harsh insult. However, little is known about SG biogenesis in renal tubular cells.

Methods

To explore how tubular cells form SGs to a series of interventions, we applied different kinds of stressors to cultured mouse (BUMPT) and rat (RPTC) proximal tubular cells as well as a short period of ischemia/reperfusion to mouse kidneys.

Results

It was found that glycolytic inhibitors such as 2DG (2-deoxy-D-glucose) and 3PO (3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one) can induce SG formation within 30 minutes in cultured BUMPT and RPTC cells. Similarly, SGs are induced by inhibitors for the respiratory chain of mitochondria such as sodium azide and CCCP (carbonyl cyanide m-chlorophenyl hydrazone). Interestingly, cisplatin, a common chemotherapy drug for many types of cancers, hardly induces SG formation. Ischemia/reperfusion to mouse kidneys can induce SG formation in renal proximal tubular cells. To further test the role of SGs in renal tubular cells, we stably knocked down G3BP1, a SG core protein, in BUMPT and RPTC cells by shRNA viral transduction. As expected, knockdown of G3BP1 partially disrupts the assembly of SGs. After azide or cisplatin treatment, more dead cells were found morphologically in knockdown cells in comparison to controls, accompanied by increment in cleaved caspase-3 expression. Re-introduction of exogenous G3BP1 into knockdown cells can rescue the cell death phenotype.

Conclusion

All taken together, SGs can form in cultured renal proximal tubular cells at certain conditions and kidneys after ischemia/reperfusion. Intervention on SG biogenesis may provide an approach to lessen the severity of a series of renal diseases.

Funding

  • NIDDK Support