Gang, W. | Search bioRxiv

bioRxiv2024

Insights into Human Epileptogenesis with Proteomic Profiling

Epilepsy affects millions globally, and drug-resistant epilepsy remains a challenge. Molecular mechanisms underlying epilepsy remain elusive. Protein profiling through proteomics offers insight into biomarkers and therapeutic targets. Human brain tissue from epilepsy surgeries was analyzed using data-independent acquisition (DIA) proteomics. Samples were categorized into Core (epileptogenic focus), Border (marginal excision tissue), and Nonepileptic control groups. Differential expression proteins (DEPs) were identified and shared proteins were analyzed. 163 DEPs were identified which may has potential roles in the initiation of epileptic electrical firing, 412 DEPs which indicating the difference between epilepsy and Nonepilepsy patients and 10 DEPs consistently altered in Core which indicating potential roles in epileptogenesis. Notably, P35754/GLRX, O75335/PPFIA4, and Q96KP4/CNDP2 were consistently expressed differently in all group pairs. From validation experiments, the expression of Kv3.2 significant reduced in the Core group compare to border group by immunohistochemistry and knockdown of Kv3.2 increased seizure susceptibility and altered neuronal excitability through our cellular and animal experimentation.

neuroscience↗

bioRxiv2023

Peripheral extracellular vesicle-derived miR-150-3p exacerbates acute kidney injury following acute pancreatitis by promoting ferroptosis through FTH1 signaling

Acute kidney injury following acute pancreatitis (AP-AKI) is one of the most fatal complications caused by acute pancreatitis (AP). Extracellular vesicles (EVs) in circulating blood are believed to be crucial to the process of AP-AKI, but the mechanisms are still unclear. In this study, we first constructed an AP-AKI rat model by retrograde sodium taurocholate through the pancreatic duct and then injected circulating blood-derived EVs into AP-AKI rats. Measurements of peripheral blood creatinine and urea nitrogen levels showed that EVs could add to kidney injury in AP-AKI rats. By analyzing the levels of renal Fe2+, cyclooxygenase 2 (COX-2), malondialdehyde (MDA), and glutathione peroxidase 4 (GPX4), we also found that extracted EVs could aggravate renal tubular ferroptosis in AP-AKI rats. Using high-throughput sequencing, we screened for high expression of EV miR-150-3P in AP-AKI patients. In vitro, we found that overexpressed miR-150-3P can influence MDA, Fe2+, lipid peroxide and GSH levels in HK-2 cells and ultimately aggravate ferroptosis. Next, through a dual-luciferase assay, we confirmed that miR-150-3p could exacerbate ferroptosis by directly targeting ferritin heavy chain 1 (FTH1). Finally, in AP-AKI rats, we again demonstrated that overexpression of miR-150-3P exacerbated renal ferroptosis through the miR-150-3P/FTH1 axis. Collectively, these findings provide new avenues to explore the mechanisms of the onset and exacerbation of AP-AKI.

cell biology↗