Ghrelin improves muscle function in dystrophin-deficient mdx mice by inhibiting NLRP3 inflammasome activation

Publication date: 1 September 2019Source: Life Sciences, Volume 232Author(s): Leilei Chang, Fengnan Niu, Jian Chen, Xiang Cao, Zhuo Liu, Xinyu Bao, Yun XuAbstractAimsImmuno-inflammation contributes to the pathogenesis of Duchenne muscular dystrophy (DMD), characterized by progressive muscle degeneration and weakness. The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is crucial for initiating innate immunity. Ghrelin is a circulating hormone that exerts anti-inflammatory activity in several inflammatory diseases. However, the role of ghrelin in DMD and underlying mechanism are still unstated. Therefore, we investigated the effect and potential mechanism of ghrelin on muscle morphology and muscular function of mdx mice, a mouse model of DMD.Main methods4-Week-old male mdx mice were injected intraperitoneally with ghrelin (100 μg/kg of body weight/day) or saline for 4 weeks. Then, muscle performance was evaluated by behavioral tests. Skeletal muscles samples were collected and relevant parameters were measured by using histopathological analysis and molecular biology techniques both in mdx muscles and primary myoblasts.Key findingsGhrelin significantly improved motor performance, alleviated muscle pathology and decreased inflammatory cell infiltration in mdx mice. Importantly, ghrelin dramatically inhibited NLRP3 inflammasome activation and reduced the production of mature IL-1β both in dystrophic muscle...
Source: Life Sciences - Category: Biology Source Type: research