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Tacrolimus-induced nephrotoxicity in tubuloids

ABSTRACT: Tacrolimus (TAC) is a first-line immunosuppressant used to prevent rejection after solid-organ transplantation, yet its clinical utility is limited by nephrotoxicity, which can progress to irreversible kidney injury or graft loss. The molecular mechanisms underlying TAC-induced nephrotoxicity remain insufficiently understood. Here, we systematically assessed TAC responses in a human in vitro nephron model: adult stem cell-derived kidney tubuloids from two donors (T19 and T30). Cell viability (CellTiter-Fluor), intracellular tacrolimus accumulation (LC-MS/MS), targeted gene expression of drug transporters and metabolizing enzymes (RT-qPCR) and whole-transcriptome responses (bulk RNA-seq) were measured, with co-treatment by P-glycoprotein (P-gp) inhibitors used to modulate intracellular tacrolimus levels.

ORGANISM(S): Homo sapiens

SUBMITTER:

PROVIDER: S-VHPS25 | biostudies-other |

REPOSITORIES: biostudies-other

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