Acute kidney injury (AKI) is a prevalent acute pathology in medical settings, but the core pathogenesis of AKI-induced acute lung injury (ALI) has not been fully elucidated, resulting in a lack of precise prevention and treatment strategies in clinical practice. Existing research often focuses on single pathological components (such as the release of inflammatory factors), with insufficient understanding of the key signaling pathways, regulatory molecules, and clinical translational value of kidney-lung cross-organ injury, hindering the development of targeted therapies. Through a three-tiered research system encompassing animal model validation, cellular mechanism analysis, and clinical sample support, the team conducted sequential studies on AKI rat models (ischemia-reperfusion), kidney-lung cell co-culture experiments, and clinical sample testing in AKI patients, focusing on the role of inflammatory regulatory pathways and effector molecules. The results of these studies confirmed activation of the TLR4/NF-κB pathway in lung tissue following AKI (TLR4 protein expression was 2.3 times higher), as well as an increased prevalence of Cit-H3, a marker for neutrophil extracellular traps (NETs). Cell experiments revealed that the apoptosis rate of HUVECs in the supernatant-treated group (H/R-SN intervention) reached (28.6±3.2)%, significantly higher than the blank group (3.1±0.5)% (P<0.01). In contrast, the apoptosis rate in the supernatant + TLR4 siRNA group decreased to (12.3±2.1)%, a 57% decrease compared to the supernatant-treated group (P<0.01). This suggests that renal DAMPs can induce apoptosis in pulmonary endothelial cells, and this effect is TLR4-dependent.

Tao Zeng, Hua Huang, Jing Zhou. Mechanism Of the Development of Acute Lung Injury After Acute Kidney Injury. International Journal of Health and Pharmaceutical Medicine (2022), Vol. 3, Issue 1: 86-95. https://doi.org/10.38007/IJHPM.2022.030108.

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