Long Non-Coding RNAs Nuclear Paraspeckle Assembly Transcript 1 Antagonist Encapsulated by Liposome Nanoparticles Regulates Macrophage Glucose Metabolism Reprogramming in Ulcerative Colitis

Abstract

This study explored the mechanism by which Long Non-Coding RNA-Nuclear Enriched Abundant Transcript 1 (LncRNA-NEAT1) antagonists encapsulated in liposome nanoparticles regulate reprogramming of macrophage glucose metabolism in ulcerative colitis (UC) patients. Sprague-Dawley (SD) rats were assigned into blank control group, UC model group, LncRNA-NEAT1 antagonist group (antagonist group) and LncRNA-NEAT1 antagonist encapsulated by liposome nanoparticles group (nano+antagonist group). Rats in the blank control group were not given any intervention, while rats in the UC model group were fully anesthetized to establish a UC model. The antagonist group was given LncRNA-NEAT1 antagonists on the basis of the UC model. Combined intervention with LncRNA-NEAT1 antagonists encapsulated by plastid nanoparticles were given to the nano+antagonist group. LncRNA-NEAT1 antagonist encapsulated by liposome nanoparticles reduced colon mucosal damage index and CMDI) score of UC rats, improving gross morphology damage of mucosa, and also reducing the pathological damage of lung tissue in the rats. The LncRNA-NEAT1 antagonist inhibited reprogramming level of glucose metabolism in macrophages, reduced consumption of cellular glucose, and further reduced lactic acid content in the macrophages. In addition, the LncRNA-NEAT1 antagonist further inhibited the expression of glycolysis-related enzymes in macrophages by inhibiting Rho associated coiled-coil containing protein kinase/Myosin streptophilic kinase (ROCK/MLCK) pathway. LncRNA-NEAT1 has a targeting relationship with ROCK/MLCK pathway. In conclusion, down-regulating NEAT1 inhibited the activity of ROCK/MLCK signaling, reducing inflammatory response, thereby repairing the intestinal barrier function, and inhibiting the reprogramming of glucose metabolism in macrophages from the UC rats. In addition, liposome nanoparticle encapsulation has broad prospects in the field of drug delivery, which can achieve the purpose of enhancing drug efficacy.