Albumin Nanoparticles Carrying miR-223 Promote Macrophages Autophagy in Pulmonary Tuberculosis Through Signal Transducer and Activator of Transcription 3 (STAT3) Pathway

Abstract

Differential expression of miR-223 is related to the progression of tuberculosis. This study mainly explored the effect of albumin nanoparticles carrying miR-223 on macrophage autophagy in tuberculosis and related mechanisms. Sixty SD rats were selected and randomly divided into (n = 10 for each, 12 mg/mL) sham group, model group, miR-223 group, isoniazid group, STAT3 pathway inhibitor group, and STAT3 pathway agonist group. The rat body weight and number of Mycobacterium tuberculosis were measured and expressions of miR-223, p-STAT3, STAT3, Beclin1, and LC3-II/LC3-I were determined. Moreover, the targeting relationship between miR-223 and STAT3 was analyzed. The difference in the rat weight between four groups was not significance in the 1st day (P > 0.05), while the weight of the model group was lowest on the 15th day, and weights of the other three groups increased significantly (P < 0.05). The number of Mycobacterium tuberculosis in the model group reached (8.58±0.22) lg10, while the number of Mycobacterium tuberculosis in the isoniazid group and miR-223 group were lower than the model group (P < 0.05). The expression of miR-223 in the model group was lower than in the other groups (P < 0.05). The expressions of p-STAT3 and STAT3 were highest but the expressions of Beclin1 and LC3-II/LC3-I were lowest in the model group (P < 0.05). The expressions of p-STAT3 and STAT3 were highest in the model and STAT3 pathway agonist groups, while expressions of Beclin1 and LC3-II/LC3-I, and the number of Mycobacterium tuberculosis were lowest, while the sham and STAT3 pathway inhibitor groups showed opposite trends (P < 0.05). Moreover, significant difference was found in comparisons between model group and STAT3 pathway agonist group (P < 0.05), but no such significance existed between the sham and STAT3 pathway inhibitor groups (P > 0.05). In conclusion, albumin nanoparticles-encapsulated miR-223 slowed release of miR-223 to the body, which directly inhibited the activity of STAT3 pathway and downregulated the expression of STAT3 and p-STAT3, but up-regulated the expression of Beclin1 and LC3-II/LC3-I expression, ultimately promoting macrophage autophagy in tuberculosis. The main mechanism for miR-223 was related to inhibition of the STAT3 pathway.