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

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Enzyme and Microbial Technology Pub Date : 2025-12-01 Epub Date: 2025-08-06 DOI:10.1016/j.enzmictec.2025.110730

Jae-Sung Ryu, Jin Ok Yu, Ki Kwan Kim, Eun-Jeong Jeong, Min Young Kim, Hyo Gyeong Yun, Eun Bin Song, Ji-Su Kim, Young-Woock Noh, Young-Kug Choo

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引用次数: 0

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.

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脂多糖对人诱导多能干细胞衍生肾类器官中神经节苷脂表达的影响。

类器官是一种自组织的三维（3D）干细胞衍生的结构，它密切模仿特定器官或组织的结构、细胞和功能特性。类器官被广泛用于评估药物的有效性、安全性和工业化学毒性。本研究的目的是利用人诱导多能干细胞（iPSCs）生成肾类器官，并通过脂多糖（LPS）处理建立脓毒症相关急性肾损伤（SA-AKI）模型。我们进一步分析了脂多糖处理后肾类器官中神经节苷脂表达的变化。结果，我们观察到在分化过程中肾脏特异性标志物的表达显著增加。接下来，我们证实了炎症相关标志物和活性氧（ROS）水平显著增加，而在lps处理的肾类器官中，线粒体膜电位（MMPΨ）显著降低。有趣的是，神经节苷脂GM3、GM2、GD3和GD1a的表达及其生物合成在lps处理的肾类器官中显著降低。这些发现表明神经节苷在炎症中起关键作用，并可能参与SA-AKI的病理生理，突出了肾类器官作为研究肾损伤和相关炎症反应的有价值的模型系统的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Enzyme and Microbial Technology 生物-生物工程与应用微生物

CiteScore

7.60

自引率

5.90%

发文量

142

审稿时长

38 days

期刊介绍： Enzyme and Microbial Technology is an international, peer-reviewed journal publishing original research and reviews, of biotechnological significance and novelty, on basic and applied aspects of the science and technology of processes involving the use of enzymes, micro-organisms, animal cells and plant cells. We especially encourage submissions on: Biocatalysis and the use of Directed Evolution in Synthetic Biology and Biotechnology Biotechnological Production of New Bioactive Molecules, Biomaterials, Biopharmaceuticals, and Biofuels New Imaging Techniques and Biosensors, especially as applicable to Healthcare and Systems Biology New Biotechnological Approaches in Genomics, Proteomics and Metabolomics Metabolic Engineering, Biomolecular Engineering and Nanobiotechnology Manuscripts which report isolation, purification, immobilization or utilization of organisms or enzymes which are already well-described in the literature are not suitable for publication in EMT, unless their primary purpose is to report significant new findings or approaches which are of broad biotechnological importance. Similarly, manuscripts which report optimization studies on well-established processes are inappropriate. EMT does not accept papers dealing with mathematical modeling unless they report significant, new experimental data.