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Abstract: SA-PO585

Lipopolysaccharide Causes Renal Biotin Uptake Inhibition via a Transcriptional Mechanism

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Ganapathy, Ashwinkumar subramenium S., Penn State Hershey Medical Center, Hershey, Pennsylvania, United States
  • Moradi, Hamid, University of California, Irvine, Orange, California, United States
  • Subramanian, Veedamali, University of California, Irvine, Orange, California, United States
  • Said, Hamid M., UCI/VA, Long Beach, California, United States
Background

Biotin (vitamin B7), a water-soluble vitamin, is indispensable for normal human health and its deficiency is associated with various severe clinical conditions. Renal proximal tubule epithelial cells are critical to maintaining normal body biotin homeostasis by mediating its reabsorption via a specific carrier mediated process (sodium-dependent multivitamin transporter [SMVT]). Although it has also been shown that lipopolysaccharides (LPS) can cause intestinal biotin deficiency by inhibiting its absorption, very little is known about the effect of inflammation and LPS on the kidney biotin uptake process.

Methods

Given the major role of inflammation in kidney disease and injury we sought to assess the effect of LPS exposure on renal biotin transport. We evaluated the impact of LPS on renal biotin uptake, expression, promoter activity and transcriptional regulation using in vitro (human proximal tubule kidney epithelial HK2 cells) and in vivo (mice) models subjected to LPS for 72 hours.

Results

The HK2 cells treated with LPS from gram negative E. coli (10 µg/ml) exhibited a significant inhibition in carrier-mediated biotin uptake, compared to controls. This inhibition was associated with a significant reduction in SMVT protein, mRNA and hnRNA expression levels. Similar inhibition of SMVT protein, mRNA and hnRNA expression levels were also observed in mice injected with LPS (2 mg/kg body weight). Additionally, we found that SLC5A6 (biotin) promoter activity was attenuated following LPS treatment of HK2 cells. This was associated with a significant reduction in the mRNA expression levels of activator protein-2 (AP-2), a transcription factor which drives the SLC5A6 promoter activity, in both of our in vitro and in vivo models.

Conclusion

This study shows for the first time that LPS inhibits renal biotin uptake via a transcriptionally-mediated mechanism. The potential clinical impact of these findings and possible role of biotin therapy in kidney injury caused by LPS remains to be determined.

Funding

  • NIDDK Support