Effect of lipopolysaccharide on ganglioside expression in human induced pluripotent stem cell-derived kidney organoids

Abstract

An organoid is a self-organizing, three-dimensional (3D), stem cell-derived structure that closely mimics the structural, cellular, and functional properties of specific organs or tissues. Organoids are widely utilized for assessing drug efficacy, safety, and industrial chemical toxicity. The purpose of this study was to generate a kidney organoid from human induced pluripotent stem cells (iPSCs) and establish a sepsis-associated acute kidney injury (SA-AKI) model by treatment with lipopolysaccharide (LPS). We further analyzed changes in ganglioside expression following LPS treatment in kidney organoids. As a result, we observed that the expression of kidney-specific markers was significantly increased during differentiation. Next, we confirmed that the levels of inflammation-related markers and reactive oxygen species (ROS) were significantly increased, whereas mitochondrial membrane potential (MMPΨ) was significantly reduced in LPS-treated kidney organoids. Interestingly, ganglioside GM3, GM2, GD3, and GD1a expression, as well as their biosynthesis, was notably decreased in LPS-treated kidney organoids. These findings suggest that gangliosides play critical roles in inflammation and may contribute to the pathophysiology of SA-AKI, highlighting the potential of kidney organoids as a valuable model system for studying kidney injury and associated inflammatory responses.