Anti-high-mobility group box-1 (HMGB1) mediates the apoptosis of alveolar epithelial cells (AEC) by receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway in the rats of crush injuries

Abstract

Objectives The lung injury is often secondary to severe trauma. In the model of crush syndrome, there may be secondary lung injury. We hypothesize that high-mobility group box 1 (HMGB1), released from muscle tissue, mediates the apoptosis of alveolar epithelial cells (AEC) via HMGB1/Receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway. The study aimed to investigate how HMGB1 mediated the apoptosis of AEC in the rat model. Methods Seventy-five SD male rats were randomly divided into five groups: CS, CS + vehicle, CS + Ethyl pyruvate (EP), CS + FPS-ZM1 group, and CS + SP600125 groups. When the rats CS model were completed after 24 h, the rats were sacrificed. We collected the serum and the whole lung tissues. Inflammatory cytokines were measured in serum samples. Western blot and RT-qPCR were used to quantify the protein and mRNA. Lastly, apoptotic cells were detected by TUNEL. We used SPSS 25.0 for statistical analyses. Results Nine rats died during the experiments. Dead rats were excluded from further analysis. Compared to the CS group, levels of HMGB1 and inflammatory cytokines in serum were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Western blot and RT-qPCR analysis revealed a significant downregulation of HMGB1, RAGE, and phosphorylated-JNK in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, excluding total-JNK mRNA. Apoptosis of AEC was used TUNEL to assess. We found the TUNEL-positive cells were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Conclusion The remote lung injury begins early after crush injuries. The HMGB1/RAGE/JNK signaling axis is an attractive target to abrogate the apoptosis of AEC after crush injuries.

BMSC-Derived Exosomes Alleviate Sepsis-Associated Acute Respiratory Distress Syndrome by Activating the Nrf2 Pathway to Reverse Mitochondrial Dysfunction

“…We noted that the HMGB1 expression in the lung tissues increased in sepsis, which could be decreased by BMSCexos. Most importantly, ML385 successfully blocked the BMSC-exos' role of alleviating the HMGB1 expression in the lung tissues, since HMGB1 expression and secretion could lead to AECII apoptosis and macrophage inflammatory response via its receptor-advanced glycation end products and TLR4 [56,57]. Besides, BMSC-exos successfully alleviated IL-6 levels in BALF serum which could be reversed with ML385.…”

Зміни Показників Ендогенної Інтоксикації У Крові Та Легенях Щурів У Динаміці Розвитку Синдрому Тривалого Стиснення

“…Щодо ураження легень при СТС, то наявні лише поодинокі клінічні спо стереження ушкодження легень після отриман ня тяжкої травми. Імовірно, ушкодження легень є вторинним відносно травми і зумовлене лейко ци тарною інфільтрацією та підвищенням рівня про запальних цитокінів у легеневій тканині [6,7]…”