Dan Liu,Hui Yu,Zhicun Liu,Le Wang,Dawo Liu,Xiangyu Cao
Acrolein is a significant high priority hazardous air pollutant. This research explore the relationship of acrolein-induced ferroptosis with the pathogenesis of lung injury by combining cellular, transcriptome, and animal-level studies. The results in vivo and in vitro models indicated that a total of 18,868 differenced lncRNAs and 15,639 differenced mRNAs were obtained after acrolein exposure. After screening, 636 lncRNAs and 214 mRNAs were obviously different of the acrolein injured group with the control group. Differential genes were mainly enriched in the iron ion binding, tissue homeostasis, etc. Among them, lncRNA MIR155HG significantly responded to the toxic effects of acrolein, the knockdown of lncRNA MIR155HG could inhibit miR-155-5p expression, promote CD200R1 expression, and improve cell viability. Furthermore, it effectively inhibited acrolein-induced the activation of ferroptosis pathway in BEAS-2B cells and lung tissue, indicating that lncRNA MIR155HG might be a potential new target for the inhibition of acrolein toxicity. LncRNA-MIR155HG/miR-155-5p/CD200R1 axis played an significant role in the lung injury, and induced ferroptosis by regulating the Nrf2/SLC7A11/GPX4 pathway. This study is the first to reveal that acrolein exposure significantly affected lncRNA and mRNA expression in BEAS-2B cells, and found that lncRNA MIR155HG effectively regulated acrolein-induced ferroptosis pathway, providing novel insights for the treatment of lung injury.
Tingwen Zhang,Ruihong Zou,Zheng Chen,Yawei Li,Xin Sun,Xialin Sun
Background Overuse of acetaminophen (APAP) can induce acute liver injury (ALI), and its mechanism is closely related to ferroptosis. 4′-O-β-D-glucosyl-5-O-methylvisamminol (5-O) is a natural coumarin glycoside with anti-inflammatory and antioxidant activities, but whether it can alleviate liver injury through intervention in ferroptosis and multi-dimensional mechanisms remains unclear. Purpose To explore whether 5-O can alleviate APAP-induced ALI through multiple mechanisms such as inhibiting ferroptosis, regulating inflammation, promoting lipid metabolism, and reshaping the intestinal microbiota . Methods Through in vitro and in vivo experiments, combined with CCK-8, Western blot, whole transcriptome sequencing, 16S rRNA sequencing, FMT and other techniques and methods, the mechanism of 5-O was evaluated from multiple levels such as cells, tissues, metabolism and flora. Results 5-O downregulated Tfrc/Slc39a14 in cells to reduce iron intake and upregulated Slc7a11/GPX4 to enhance antioxidant capacity. It reduced serum ALT/AST, alleviated liver tissue pathological damage, inhibited the expression of chemokines and inflammatory factors, and activated the PPARα-Fabp1/Me1 axis to promote lipid metabolism. Whole transcriptome analysis revealed that 5-O intervention was associated with upregulation of miR-30e-3p and downregulation of Tfrc, suggesting a potential role in modulating iron metabolism. Concurrently, the analysis indicated that 5-O treatment was linked to inhibition of the ferroptosis pathway and activation of the PPAR pathway. In addition, 5-O reshaped the intestinal microbiota, inhibited pro-inflammatory bacterial genera, and promoted the colonization of the probiotic Lactobacillus . Conclusion This study systematically clarified that the hepatoprotective effect of 5-O against APAP-induced liver injury is associated with a multi-dimensional network involving "ferroptosis-inflammation-metabolism-flora". The innovation lies in systematically elucidating the multi-faceted actions of a natural product, which may involve regulating ferroptosis through miR-30e-3p associated changes, cross-organ metabolic reprogramming, and microecological modulation. This work provides a candidate drug with multi-dimensional synergistic potential for the prevention and treatment of liver injury.
危险品化学品经营许可证（带存储）