The role of FPR2-mediated ferroptosis in formyl peptide-induced acute lung injury against endothelial barrier damage and protective effect of the mitochondria-derived peptide MOTS-c.

BACKGROUND: Acute lung injury (ALI) has garnered significant attention in the field of respiratory and critical care due to its high mortality and morbidity, and limited treatment options. The role of the endothelial barrier in the development of ALI is crucial. Several bacterial pathogenic factors, including the bacteria-derived formyl peptide (fMLP), have been implicated in damaging the endothelial barrier and initiating ALI. However, the mechanism by which fMLP causes ALI remains unclear. In this study, we aim to explore the mechanisms of ALI caused by fMLP and evaluate the protective effects of MOTS-c, a mitochondrial-derived peptide. METHODS: We established a rat model of ALI and a human pulmonary microvascular endothelial cell (HPMVEC) model of ALI by treatment with fMLP. In vivo experiments involved lung histopathology assays, assessments of inflammatory and oxidative stress factors, and measurements of ferroptosis-related proteins and barrier proteins to evaluate the severity of fMLP-induced ALI and the type of tissue damage in rats. In vitro experiments included evaluations of fMLP-induced damage on HPMVEC using cell activity assays, assessments of inflammatory and oxidative stress factors, measurements of ferroptosis-related proteins, endothelial barrier function assays, and examination of the key role of FPR2 in fMLP-induced ALI. We also assessed the protective effect of MOTS-c and investigated its mechanism on the fMLP-induced ALI in vivo and in vitro. RESULTS: Results from both in vitro and in vivo experiments demonstrate that fMLP promotes the expression of inflammatory and oxidative stress factors, activates ferroptosis and disrupts the vascular endothelial barrier, ultimately contributing to the development and progression of ALI. Mechanistically, ferroptosis mediated by FPR2 plays a key role in fMLP-induced injury, and the Nrf2 and MAPK pathways are involved in this process. Knockdown of FPR2 and inhibition of ferroptosis can attenuate ALI induced by fMLP. Moreover, MOTS-c could protect the vascular endothelial barrier function by inhibiting ferroptosis and suppressing the expression of inflammatory and oxidative stress factors through Nrf2 and MAPK pathways, thereby alleviating fMLP-induced ALI. CONCLUSION: Overall, fMLP disrupts the vascular endothelial barrier through FPR2-mediated ferroptosis, leading to the development and progression of ALI. MOTS-c demonstrates potential as a protective treatment against ALI by alleviating the damage induced by fMLP.

LNC01296 Regulates Apoptosis Genes Birc2 and Bak1 by Targeting miRNA-29c and Participates in Neuroprotection During Cerebral Ischemia/Reperfusion Injury in Rats.

AIM: To explore the extent to which LNC01296 inhibits the miRNA-29c expansion genes Birc2 and Bak1 from causing damage induced by brain expansion and reimplantation. MATERIAL AND METHODS: A total of 120 adult male experimental rats were divided to verify the effects of miRNA-29c and LNC01296 on brain expansion/reimplantation injury. RESULTS: miRNA-29c can inhibit the Birc2/Bak1 pathway and aggravate the brain expansion/reimplantation damage. LNC01296 blocks miRNA-29c from entering the brain to protect it from expansion after reimplantation. CONCLUSION: Our findings show that LINC01296 can alleviate the injury induced by cerebral ischemia and reimplantation by preventing the inhibitory effect of miR-29c on Birc2 and Bak1. Our research also provides new strategies and goals for the clinical treatment of patients with cerebral ischemia?reperfusion.