Resistant Starch Nanoparticles Induce Colitis through Lysosomal Exocytosis in Mice

IF 15.8 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY ACS Nano Pub Date : 2024-10-23 DOI:10.1021/acsnano.4c1048110.1021/acsnano.4c10481
Chenglu Peng, Wei Lu*, Ran An, Xiaoyang Li, Cuixia Sun and Yapeng Fang*, 
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Abstract

Resistant starch (RS) is present in various natural and processed foods as well as medications. It has garnered significant attention from both scientists and consumers due to its notable health benefits. However, there is a limited understanding of how RS particles are absorbed at the cellular level and their metabolic behavior, resulting in a lack of clarity regarding the intestinal safety implications of prolonged RS exposure. Here, we demonstrate that rice-derived RS nanoparticles (RSNs) can lead to colitis in mice by triggering lysosomal exocytosis. The research shows that RSNs enter the cells through macropinocytosis and clathrin- and caveolin-mediated endocytosis and activate TRPML1 thereafter, causing the release of lysosomal calcium ions. This, in turn, triggered the TFEB signaling pathway and thus upregulated the lysosomal exocytosis level, leading to lysosomal enzymes to be released to the intestinal lumen. As a result, a decreased number of intestinal goblet cells, diminished tight junction protein expression, and imbalanced intestinal flora in mice were observed. These damages to the intestinal barrier ultimately led to the occurrence of colitis. Our study offers important insights into the cellular bioeffects and detrimental effects on intestinal health caused by RS particles and emphasizes the need to re-evaluate the safety of long-term RS consumption.

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抗性淀粉纳米颗粒通过溶酶体外泌作用诱发小鼠结肠炎
抗性淀粉(RS)存在于各种天然食品、加工食品和药物中。由于其对健康的显著益处,它受到了科学家和消费者的极大关注。然而,人们对 RS 颗粒如何在细胞水平被吸收及其新陈代谢行为的了解十分有限,因此对长期接触 RS 对肠道安全的影响缺乏明确的认识。在这里,我们证明了大米衍生的 RS 纳米粒子(RSNs)可通过触发溶酶体外渗导致小鼠结肠炎。研究表明,RSNs 通过大蛋白胞吞、凝集素和洞穴素介导的内吞作用进入细胞,随后激活 TRPML1,导致溶酶体钙离子释放。这反过来又触发了 TFEB 信号通路,从而上调了溶酶体的外泌水平,导致溶酶体酶被释放到肠腔。结果,观察到小鼠肠道鹅口疮细胞数量减少、紧密连接蛋白表达减弱以及肠道菌群失调。这些对肠屏障的破坏最终导致了结肠炎的发生。我们的研究为了解 RS 颗粒的细胞生物效应和对肠道健康的不利影响提供了重要启示,并强调有必要重新评估长期食用 RS 的安全性。
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来源期刊
ACS Nano
ACS Nano 工程技术-材料科学:综合
CiteScore
26.00
自引率
4.10%
发文量
1627
审稿时长
1.7 months
期刊介绍: ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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