Abstract
Primary blast lung injury (PBLI) is a common cause of casualties in wars, terrorist attacks, and explosions. It can exist in the absence of any other outward signs of trauma, and further develop into acute lung injury (ALI) or a more severe acute respiratory distress syndrome (ARDS). The pathogenesis of PBLI at the cellular and molecular level has not been clear. Damage-associated molecular pattern (DAMP) is a general term for endogenous danger signals released by the body after injury, including intracellular protein molecules (HMGB1, histones, s100s, heat shock proteins, eCIRP, etc.), secretory protein factors (IL-1β, IL-6, IL-10, TNF-α, VEGF, complements, etc.), purines and pyrimidines and their derived degradation products (nucleic acids, ATP, ADP, UDPG, uric acid, etc.), and extracellular matrix components (hyaluronic acid, fibronectin, heparin sulfate, biglycan, etc.). DAMPs can be detected by multiple receptors including pattern recognition receptors (PRRs). The study of DAMPs and their related signaling pathways, such as the mtDNA-triggered cGAS-YAP pathway, contributes to revealing the molecular mechanism of PBLI, and provides new therapeutic targets for controlling inflammatory diseases and alleviating their symptoms. In this review, we focus on the recent progress of research on DAMPs and their signaling pathways, as well as the potential therapeutic targets and future research directions in PBLI.
Highlights
Explosions often occur in modern wars, terrorist attacks, or daily emergencies, and blast injury is a common cause of casualties [1,2]
Most TLRs are recruited by mTyLeRlosidardeiffloecraetnetdiaotinonthpercoetlelinsu8r8fa(cMe oyrDi8n8s)id-deetpheencdeelln, tanILd-1carnecreepctoogrn-aizsesoDciAatMedPskisnuacshea(sIRAK), wnuhciclehicthaecnidasc, tHivMatGesBn1u, hcleeaatrsfhaoctcokrp-κrBot(eNinFs-κ(HB)StPos)p,raonmdoSt1e0in0flparmotmeinatso. rMyorestspToLnRsse(beyxcuepprteTgLuRla3t)ing the are recruited by myeloid differentiation protein 88 (MyD88) -dependent IL-1 receptorassociated kinase (IRAK), which activates nuclear factor-κB (NF-κB) to promote expression of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-8 [40,47]
Receptor for advanced glycation end products receptor for advanced glycation end products (RAGE) is a transmembrane protein that belongs to the immunoglobulin receptor superfamily and is expressed by multiple cell types, including neutrophils, monocytes, smooth muscle cells, endothelial cells, and cancer cells, and mediates cell response to Damage-associated molecular pattern (DAMP) such as HMGB1, S100 proteins, advanced glycation end products (AGEs), and DNA to promote the expression of pro-inflammatory genes, as well as cell migration, proliferation, and apoptosis [63]
Summary
Explosions often occur in modern wars, terrorist attacks, or daily emergencies, and blast injury is a common cause of casualties [1,2]. The blast wave-induced acute lung injuries (ALI) are generally closed wounds rather than traditional penetrating wounds, which can be sustained in the absence of any other external signs of thoracic trauma [6]. It may further develop into acute respiratory distress syndrome (ARDS), a more severe physiological expression of ALI [11]. Damage-associated molecular pattern (DAMP) was first proposed by Land in 2003 [12] It is the general term for endogenous risk signals released by the organism after injury, which can trigger non-infectious and uncontrolled inflammation in the body [13,14], aggravating the lung tissue damage after an explosion [15]. This review will focus on DAMPs and their signaling pathways related to PBLI, and explore possible therapeutic targets in future clinical treatment
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