Objective: This study aimed to elucidate the functional role of Kininogen-1 (KNG1) in traumatic brain injury (TBI) and evaluate its potential as a therapeutic target. Methods: A TBI rat model was established using a controlled cortical impact method. Neurological deficits were assessed via modified neurological severity scores (mNSS). Brain tissues were analyzed for edema, inflammation, and neuronal damage using histopathology (HE/Nissl staining), RT-qPCR, and transcriptomics. An in vitro oxidative stress model was constructed using H 2 O 2 -treated PC-12 cells. KNG1 knockdown was achieved via siRNA transfection, followed by analysis of oxidative stress markers (ROS, SOD, CAT) and MAPK pathway activation (Western blot). Results: TBI rats exhibited significant neurological impairment. Transcriptomics identified 1,655 differentially expressed genes (DEGs), including upregulated KNG1, associated with inflammation and MAPK signaling. In vitro, KNG1 knockdown reduced oxidative stress (↑SOD/CAT, ↓ROS) and suppressed MAPK-p38/ERK phosphorylation. Conclusion: Our transcriptomic analysis of TBI rat brain tissue identified KNG1 as a significantly upregulated gene functionally linked to the MAPK pathway, suggesting its potential role as an upstream regulator. Subsequently, in vitro functional validation demonstrated for the first time that KNG1 knockdown concurrently alleviated oxidative stress and suppressed MAPK hyperactivation. Therefore, this study not only defines a critical role for KNG1 in TBI pathology but also supports its potential as a therapeutic target that modulates multiple injury cascades. Keywords: KNG1, traumatic brain injury, oxidative stress, MAPK pathway, therapeutic target
Li et al. (2026) studied this question.