Inflammation in Duchenne Muscular Dystrophy–Exploring the Role of Neutrophils in Muscle Damage and Regeneration

Abstract

Duchenne muscular dystrophy (DMD) is a severe and progressive, X-linked, neuromuscular disorder caused by mutations in the dystrophin gene. In DMD, the lack of functional dystrophin protein makes the muscle membrane fragile, leaving the muscle fibers prone to damage during contraction. Muscle degeneration in DMD patients is closely associated with a prolonged inflammatory response, and while this is important to stimulate regeneration, inflammation is also thought to exacerbate muscle damage. Neutrophils are one of the first immune cells to be recruited to the damaged muscle and are the first line of defense during tissue injury or infection. Neutrophils can promote inflammation by releasing pro-inflammatory cytokines and compounds, including myeloperoxidase (MPO) and neutrophil elastase (NE), that lead to oxidative stress and are thought to have a role in prolonging inflammation in DMD. In this review, we provide an overview of the roles of the innate immune response, with particular focus on mechanisms used by neutrophils to exacerbate muscle damage and impair regeneration in DMD.

Analysis of Long Noncoding RNAs-Related Regulatory Mechanisms in Duchenne Muscular Dystrophy Using a Disease-Related lncRNA-mRNA Pathway Network

“…Tus, this study provides important insights into the underlying mechanisms of lncRNAs in the pathogenesis of DMD and provides potential targets that could aid in the rational design of lncRNA-based therapies for DMD. Lack of dystrophin results in chronic infammation, which is closely associated with muscle degeneration in the pathogenesis of DMD [19,20]. In our proposed DMDrelated lncRNA-mRNA pathway networks, PYCARD, RIPK2, and CASP1 were signifcantly enriched in the NODlike receptor signaling pathway, whereas MAP2K2, LUM, RPS6, PDCD4, TWIST1, and HIF1A were signifcantly enriched in proteoglycans in cancers.…”

P2X7 Receptor Antagonist Reduces Fibrosis and Inflammation in a Mouse Model of Alpha-Sarcoglycan Muscular Dystrophy

“…In particular, proinflammatory monocytes CD11b + /Ly6G − /Ly6c + have been reported to be the first innate immune cells to be mobilized from the bone marrow into the circulation and recruited to the site of tissue injury [50], such as dystrophic muscles, where they differentiated into inflammatory macrophages [51,52]. Different studies demonstrated that neutrophils actively participated in the exacerbation of muscular dystrophy and their specific depletion reduced muscular necrosis and inflammation in mdx mice [53][54][55]. Moreover, neutrophil-derived elastase impaired myoblast proliferation, survival and differentiation [56].…”

Identification of Auxiliary Biomarkers and Description of the Immune Microenvironmental Characteristics in Duchenne Muscular Dystrophy by Bioinformatical Analysis and Experiment

“…Although mechanical damage and cell membrane defects are known to be basic pathological changes in DMD, the infiltration of immune cells also has a significant impact on the occurrence and progression of DMD (Tidball et al, 2018). In particular, the immune environment of the muscle tissue in DMD patients is known to restrict the therapeutic effects of some promising treatments, such as gene editing and stem cell transplantation (Duan et al, 2021;Tulangekar and Sztal, 2021). Therefore, exploring potential diagnostic biomarkers and characterizing the infiltration pattern of immune cells in DMD is of great significance to enhance the diagnosis and prognosis of DMD (Mendell et al, 2010).…”