Role of Exosomal miR‐223 in Chronic Skeletal Muscle Inflammation

Abstract

As skeletal muscle is one of the largest organs in the body, its damage can directly reflect a decline in somatic function, thus, further affecting daily life and health. Inflammation is a prerequisite for the repair of injured skeletal muscles. Chronic inflammation induced by inadequate repair in skeletal muscle aggravates tissue injury. Exosomes regulate inflammatory responses to facilitate the repair of skeletal muscle injury. Moreover, exosomal miR‐223 with high specificity is the most abundant miRNA in peripheral blood and regarded as biomarkers for inflammation post skeletal muscle injury, which warrants further investigation. Available studies have demonstrated that exosomal miR‐223 negatively correlates with TNF‐α levels in serum and regulates the canonical inflammatory NF‐κB signaling pathway. miR‐223 is a negative feedback regulator with great potential for adjusting inflammatory imbalance and promoting skeletal muscle repair. The research on the regulation of negative feedback factors in the inflammatory signaling pathway is essential in biology and medicine. Therefore, this review mainly elaborates the formation, heterogeneity and markers of exosomes and points out exosomal miR‐223 as a beneficial role in chronic skeletal muscle inflammation and can be expected to be a potential therapeutic target for skeletal muscle damage.

Engineering extracellular vesicles for ROS scavenging and tissue regeneration

“…EVs offer a promising avenue to indirectly guide the repair of skeletal muscle tissue in many cases.Engineered EVs can be customized with specific cargos, including growth factors, microRNAs, or proteins, known to stimulate myogenic activity [275]. These bioactive payloads have the potential to promote satellite cell activation, muscle cell differentiation, and overall tissue repair [276][277][278]. For instance, previous studies have demonstrated that myomiRs like miR-206, miR-133a, and miR-1 play crucial roles in myoblast proliferation [279].…”

“…Additionally, in case of chronic inflammation followed by skeletal muscle injury, EV miR-223, the most abundant miRNA in peripheral blood, has been implicated in modulating the inflammatory response to skeletal muscle damage [280][281][282][283]. Studies have demonstrated that miR-223 down-regulates the expression of TNF-α and other pro-inflammatory molecules, inhibits inflammatory cell infiltration, and decreases the extent of necrotic muscle tissue [278,284]. Consequently, miR-223 holds promise as a potential biomarker and therapeutic target for addressing chronic inflammation associated with inadequate muscle regeneration and repair following injury.…”

Advances in Therapeutic Applications of Extracellular Vesicles

“…Current research focuses on mesenchymal stem cells, which are considered the "bank" of regenerative medicine due to their ability to evade the immune system, selfregenerate, and differentiate into various cell types with greater specificity than differentiated cells. [68][69][70] However, safety concerns have been raised regarding stem cell therapy, including ethical issues and the risk of teratoma formation with embryonic stem cell therapy, genomic instability and tumorigenesis with pluripotent stem cell therapy, and promoting tumor growth, metastasis, and differentiation into non-target tissues with mesenchymal stem cell therapy. [71][72][73][74][75] Encouragingly, recent evidence suggests that stem cells may exhibit beneficial effects through the EVs they release, playing a role similar to stem cells in tissue regeneration and damage repair.…”

Inhibition of TNF-α Restores Muscle Force, Inhibits Inflammation, and Reduces Apoptosis of Traumatized Skeletal Muscles

“…Additionally, apoptotic and necrotic effects initiated by TNF-α during skeletal muscle injury negatively affect the contractile properties of the injured muscle [ 4 ]. Long-term release of TNF-α continuously activates the NF-κB signaling cascade, which forms a vicious cycle that results in a chronic inflammation [ 5 ].…”