The Mechanosensitive Ion Channel PIEZO1 in Intestinal Epithelial Cells Mediates Inflammation through the NOD-Like Receptor 3 Pathway in Crohn’s Disease

作者：Qiuyuan Liu, WANG Didi, Xiaodong Yang, Fang Ma, Wei Han, Jing Hu, Qiao Mei · 发表于：Inflammatory Bowel Diseases · 年份：2022 · DOI：10.1093/ibd/izac152 · 被引用次数：51 · 研究领域：Erythrocyte Function and Pathophysiology、Blood properties and coagulation、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

BACKGROUND: Crohn's disease (CD) is an incurable chronic intestinal inflammatory disease with no recognized cause. It has been reported that the mechanosensitive ion channel PIEZO1 initiates proinflammatory responses. However, little is known about the role of PIEZO1 in CD. METHODS: Ileum biopsies were obtained from 30 patients with CD and 15 healthy volunteers. Clinical data were collected to determine the relationship between CD and PIEZO1. First, HT29 cells were incubated with Yoda1 and GsMTx4 (Grammostola spatulata mechanotoxin 4) to activate and inhibit PIEZO1, respectively. Second, PIEZO1 knockdown was performed using small interfering RNA. Third, calcium imaging, flow cytometry, and immunofluorescence were used to detect intracellular calcium and mitochondrial function. Last, real-time quantitative polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to quantify PIEZO1, proinflammatory cytokines, and NLRP3 (NOD-like receptor 3)-related compounds. RESULTS: PIEZO1 was highly expressed in the ileum of patients with CD and correlated positively with the Crohn's Disease Activity Index, platelet count, and hematocrit and fecal calprotectin levels. In HT29 cells, Yoda1 triggered calcium influx, which was inhibited by GsMTx4 treatment and small interfering RNA-mediated PIEZO1 knockdown. Increased calcium concentrations resulted in increased reactive oxygen species accumulation and decreased mitochondrial membrane potential, whereas decreas...