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Ming-Chieh Ma, Ph.D.

College of Medicine


School of Medicine

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Effect of Uremic Toxin Indoxyl Sulfate on Renal Tubular Damage via TRPV1 Hyperfunctioning

The uremic toxin indoxyl sulfate (IS) is known to accumulate in chronic kidney disease (CKD) patients and harm the renal tubular cells. Transient receptor potential vanilloid 1 (TRPV1) is present in the kidney and acts as a renal sensor. However, the mechanism underlying IS-mediated renal tubular damage in view of TRPV1 is lacking. We showed that hyperfunction of calcium-permeable TRPV1 contributes to the IS-mediated tubulotoxicity. IS activated aryl hydrocarbon receptor (AhR) and then upregulated 12-lipoxygenase (ALOX12), and this induced endovanilloid 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) synthesis and contributed to TRPV1 hyperfunction. These indicate that calcium overload participates in the IS-induced cell damage.