Hypoxic preconditioning protects against ischemic kidney injury through the IDO1/kynurenine pathway
Rafael Torosyan, Shengping Huang, Prashant V. Bommi, Ratnakar Tiwari, Si Young An, Michael Schonfeld, Ganeshkumar Rajendran, Matthew A. Kavanaugh, Benjamin K. Gibbs, Agnieszka D. Truax, Samuel Bohney, M. Wade Calcutt, Evan W. Kerr, Roberta Leonardi, Peng Gao, Navdeep S. Chandel, Pinelopi P. Kapitsinou
Abstract
in the post-ischemic kidney. Furthermore, we show that indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic increase of kynurenine and the subsequent renoprotection generated by hypoxic preconditioning and PHD inhibition. Importantly, exogenous administration of kynurenine restores the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our findings demonstrate a critical role of the IDO1-kynurenine axis in mediating hypoxic preconditioning.