Inhibitor of prolyl-tRNA synthetase (PRS) to reduce tubulointerstitial nephritis

Glutamyl-prolyl-transfer RNA synthetase (EPRS) is a class of enzymes that catalyze the attachment of 2 amino acids (i.e., glutamic acid and proline) to cognate transfer RNA for subsequent protein synthesis. Herein, we evaluated the effect of EPRS on the progression of tubulointerstitial nephritis using the mouse model with adenine-mixed diet. One single-cell RNA transcriptomic dataset was originated from wild-type mice, and other one was from heterozygous knockout mice, all of these were harvested at 2 weeks after adenine-mixed diet. Whole kidneys of C57BL/6 male (Eprs+/- and Eprs+/+) mice were prepared for scRNA. For a toxin-induced TIN model, mice were treated with AD and harvested at the indicated time points after reperfusion. To block the EPRS function, EPRS-targeting small molecule inhibitor was administered via peritoneal injection once daily.