Work

Discovery of kidney disease targets using multimodal human podocyte injury models

Year: 2026

Type: article

Abstract: Podocyte injury is a hallmark of chronic kidney disease (CKD) and organ failure, but whether different injury signals perturb unified or distinct molecular targets remains unclear. Using human induced pluripotent stem cell (hiPSC)-derived podocytes, we modeled cellular injury via exposure to diabetic, inflammatory, chemical toxin, biomechanical, and infectious stressors. Transcriptomic analysis revealed both shared and unique changes in gene expression across injury modes. While drug-induced injuries triggered broader transcriptional responses, conserved pathways related to lysosome function, RNA metabolism, and immune activation were identified across models. Importantly, we discovered NEU1, CD82, ABI3BP, and ADAM17 as targets of human podocyte injury. Analysis of multiple kidney disease patient biopsies confirmed enrichment of these targets, underscoring their in vivo relevance and potential as therapeutic targets. These findings highlight the predictive power of human-relevant experimental models and provide insight into podocyte injury responses, offering a framework for future precision medicine approaches.

Source: Stem Cell Reports

DOI: 10.1016/j.stemcr.2026.102868

Authors: Amanda D. Barreto, Bowen Jiang, Morgan A. Burt, Nikolaos Dimitrakakis, Samira Musah

Institutions: Duke University, Harvard University, Wyss Institute for Biologically Inspired Engineering, Duke Medical Center

Language: English

Topic: Renal Diseases and Glomerulopathies

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,190