Sepsis-Associated Muscle Wasting: A Comprehensive Review from Bench to Bedside

Abstract

Sepsis-associated muscle wasting (SAMW) is characterized by decreased muscle mass, reduced muscle fiber size, and decreased muscle strength, resulting in persistent physical disability accompanied by sepsis. Systemic inflammatory cytokines are the main cause of SAMW, which occurs in 40–70% of patients with sepsis. The pathways associated with the ubiquitin–proteasome and autophagy systems are particularly activated in the muscle tissues during sepsis and may lead to muscle wasting. Additionally, expression of muscle atrophy-related genes Atrogin-1 and MuRF-1 are seemingly increased via the ubiquitin–proteasome pathway. In clinical settings, electrical muscular stimulation, physiotherapy, early mobilization, and nutritional support are used for patients with sepsis to prevent or treat SAMW. However, there are no pharmacological treatments for SAMW, and the underlying mechanisms are still unknown. Therefore, research is urgently required in this field.

Loss of HNRNPU in Skeletal Muscle Increases Intramuscular Infiltration of Ly6C Positive Cells, leading to Muscle Atrophy through Activation of NF‐κB Signaling

“…[44] For example, systemic inflammation, including sepsis, triggers muscle atrophy via increased proinflammatory cytokines such as TNF-𝛼, IL-6, and IL-1. [45][46][47] Chronic inflammation aggravates muscle weakness and fibrosis in Duchenne muscular dystrophy. [48] Relieving inflammation improves muscle function and reduces muscle fibrosis in mdx mice, a wellknown mouse model of Duchenne muscular dystrophy.…”

Skeletal Muscle Mitochondrial Dysfunction Mediated byPseudomonas aeruginosaQuorum Sensing Transcription Factor MvfR: Reversing Effects with Anti-MvfR and Mitochondrial-Targeted Compounds

“…Critically ill patients, like cystic fibrosis and patients with burns, are highly prone to P. aeruginosa infections, augmenting the adverse effects of these pathologies on skeletal muscle (18)(19)(20). Especially because skeletal muscle constitutes 40% of total body weight and plays numerous vital roles in the human body, including movement, posture maintenance, breathing facilitation, and safeguarding internal organs (21).In previous studies, we have shown that the P. aeruginosa quorum sensing (QS) transcription factor MvfR (Multiple virulence factor Regulator) (22,23), also known as PqsR, is a central QS regulator that controls the expression of multiple virulence genes and the synthesis of many small signalling molecules in this pathogen. MvfR is required for P. aeruginosa full virulence (24)(25)(26).…”

Skeletal muscle mitochondrial dysfunction mediated by Pseudomonas aeruginosa quorum-sensing transcription factor MvfR: reversing effects with anti-MvfR and mitochondrial-targeted compounds

“…Critically ill patients, like cystic fibrosis and patients with burns, are highly prone to Pseudomonas aeruginosa infections, augmenting the adverse effects of these pathologies on skeletal muscle ( 18 – 20 ). Especially because skeletal muscle constitutes 40% of total body weight and plays numerous vital roles in the human body, including movement, posture maintenance, breathing facilitation, and safeguarding internal organs ( 21 ). In previous studies, we have shown that the P. aeruginosa quorum-sensing (QS) transcription factor MvfR (multiple virulence factor regulator) ( 22 , 23 ), also known as PqsR, is a central QS regulator that controls the expression of multiple virulence genes and the synthesis of many small signaling molecules in this pathogen.…”