Resistant Starch Nanoparticles Induce Colitis through Lysosomal Exocytosis in Mice

胞吐 结肠炎 纳米颗粒 细胞生物学 材料科学 纳米技术 化学 生物物理学 分泌物 生物化学 免疫学 生物
作者
Chenglu Peng,Wei Lü,Ran An,Xiaoyang Li,Cuixia Sun,Yapeng Fang
出处
期刊:ACS Nano [American Chemical Society]
标识
DOI:10.1021/acsnano.4c10481
摘要

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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