Genetic disruption of the inflammasome adaptor ASC has minimal impact on the pathogenesis of Duchenne muscular dystrophy in mdx mice

LIFE SCIENCES

卷:257

Article

Lau, Yeh Siang^1,2  Zhao, Lixia¹  Zhang, Chen¹  Li, Haiwen¹  Han, Renzhi¹ 

[1] Ohio State Univ, Wexner Med Ctr, Davis Heart & Lung Res Inst, Dept Surg,Biomed Sci Grad Program,Biophys Grad Pr, Columbus, OH 43210 USA

[2] Sunway Univ, Sch Healthcare & Med Sci, Bandar Sunway 47500, Selangor, Malaysia

关键词: ASC;    DMD;    mdx mice;    Inflammasome;    Inflammation;    Muscle regeneration;   

DOI  :  10.1016/j.lfs.2020.118069

来源: Elsevier

【 摘 要 】

Aim: Up-regulation of inflammasome proteins was reported in dystrophin-deficient muscles. However, it remains to be determined whether inflammasome activation plays a role in the pathogenesis of Duchenne muscular dystrophy. This study was therefore set out to investigate whether genetic disruption of the inflammasome pathway impacts the disease progression in mdx mice. Main methods: Mice deficient in both dystrophin and ASC (encoded by Pycard [PYD And CARD Domain Containing]) were generated. The impact of ASC deficiency on muscular dystrophy of mdx mice were assessed by measurements of serum cytokines, Western blot, real-time PCR and histopathological staining. Key findings: The pro-inflammatory cytokines such as TNF-alpha, IL-6, KC/GRO and IL-10 were markedly increased in the sera of 8-week-old mdx mice compared to WT. Western blotting showed that P2X7, caspase-1, ASC and IL 18 were upregulated. Disruption of ASC and dystrophin expression in the mdx/ASC(-/-) mice was verified by Western blot analysis. Histopathological analysis did not find significant alterations in the muscular dystrophy phenotype in mdx/ASC(-/-) mice as compared to mdx mice. Significance: Taken together, our results show that disruption of the central adaptor ASC of the inflammasome is insufficient to alleviate muscular dystrophy phenotype in mdx mice.

【 授权许可】

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