The Contribution of Muscle Innate Immunity to Uremic Cachexia.
Pasquale EspositoDaniela VerzolaMichela SaioDaniela PicciottoMarco FrascioAlessandro LaudonValentina ZanettiGiuliano BrunoriGiacomo GaribottoFrancesca ViazziPublished in: Nutrients (2023)
Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, "sterile" muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering "sterile" tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.
Keyphrases
- toll like receptor
- inflammatory response
- skeletal muscle
- low grade
- oxidative stress
- nuclear factor
- insulin resistance
- chronic kidney disease
- immune response
- nlrp inflammasome
- lps induced
- lipopolysaccharide induced
- signaling pathway
- stem cells
- dna damage
- metabolic syndrome
- single cell
- mesenchymal stem cells
- patient safety
- diabetic rats
- endothelial cells
- cancer therapy
- bone marrow
- cell cycle arrest
- drug induced
- cell proliferation
- binding protein
- amino acid