Dendrobium officinale polysaccharide (DOP) attenuates inflammatory bowel disease (IBD), but its role in regulating cross-talk between intestinal epithelial cells (IEC) and macrophages against IBD is unclear. This study aimed to investigate DOP protective effects on the intestinal inflammatory response through regulation by miRNA in small extracellular vesicles (sEVs). Our results show that DOP interfered with the secretion of small extracellular vesicles (DIEs) by IEC, which reduced the levels of inflammatory mediators. Increased miR-433-3p expression in DIEs was identified as an important protector against intestinal inflammation. DOP regulated the loading of miR-433-3p by hnRNPA2B1 into the intestinal sEV to increase the abundance of miR-433-3p. DIEs delivered miR-433-3p to lipopolysaccharide-induced macrophages and targeted the MAPK8 gene, leading to inhibition of the MAPK signaling pathway and reduced production of inflammatory cytokines. One protective mechanism of DOP is mediated by intestinal sEV containing miR-433-3p, which is a potential therapeutic agent for the prevention of inflammatory factor accumulation from excessive intestinal macrophage activity and for restoring homeostasis in the intestinal microenvironment.
Bibliographical noteFunding Information:
The work was financed by the Fundamental and Applied Basic Research Fund for Science and Technology Planning Project of Guangzhou (Project no. 202002030383), National Natural Science Fund of China (Project no. 32001622), National Key Research and Development Program of China (Project no. 2018YFC1602101 and 2018YFD0901003), Fundamental and Applied Basic Research Fund for Young Scholars of Guangdong Province (Project no. 2019A1515110823), Science and Technology Commissioner Project of Guangzhou (Project no. GZKTP201937), Guangdong University Youth Innovation Talent Project (Project no. KA2001957), and Science and Technology Project of Heyuan (no. 2019003). The Key Fundamental and Applied Basic Research Fund of Jiangmen City.
- Dendrobium officinale polysaccharide
- inflammatory bowel disease
- intestinal small extracellular vesicles