Effect of AAV9-hIGF-1 on inflammatory reaction in mdx mice and its mechanism

Am J Transl Res. 2020 Aug 15;12(8):4488-4497. eCollection 2020.

Abstract

This study aimed to the role of insulin-like growth factor 1 (IGF-1) in Duchenne muscular dystrophy (DMD), the inflammatory response and the potential mechanism of the effect hIGF1 exerted in muscle inflammation were also been explored. In this study, AAV9, a carrier of the human IGF-1 gene, was injected into mdx mice to observe the role of IGF-1 in DMD. Routine histopathological staining, immunofluorescence and western blot were used to detect the inflammatory response. In addition, we also explored the potential mechanism of the role of hIGF1 in muscle inflammation. The expression of AAV9 in myocardium and muscle tissue of AAV9-GFP group was detected by GFP method. GFP was expressed in different tissues of mdx mice, especially in anterior tibial muscle, triceps muscle and other tissues. The percentage of anterior tibial muscle inflammation area in CD68 and AAV9-hIGF-1 group was lower than that in AAV-GFP group, and the percentage of anterior tibial muscle inflammation area in AAV9-hIGF-1 group (1.78 ± 0.47%) was significantly lower than that in AAV GFP group (3.4 ± 1.22%) (P < 0.05). Western-blot showed that AAV-hIGF-1 group (0.45 + 0.07%) was lower than that of AAV-GFP group (0.76 + 0.13%), higher than the normal group (0.38 + 0.06%). The difference was statistically significant (P < 0.05). In conclusion, this study confirmed that hIGF-1 can reduce the inflammatory response and macrophage infiltration in mdx mice, and further proved that hIGF-1 can down regulate the expression of NF-κB signal pathway, which has anti-inflammatory effect.

Keywords: AAV9; IGF1; inflammatory; mice.