Research trends and cellular targets of NF-κB pathway in acute lung injury [2005-2024]: a combined bibliometric analysis and systematic review.

BACKGROUND: The nuclear factor-κB (NF-κB) pathway is a key regulator of inflammation and immune responses in acute lung injury (ALI). Despite significant progress in elucidating the molecular and cellular mechanisms of the NF-κB pathway in ALI, current research is scattered across different disciplines, experimental models, and cell types. Therefore, this study aims to integrate bibliometric trends with an in-depth review of molecular mechanisms to characterize publication trends, collaboration networks, and evolving research themes over the past two decades. METHODS: Literature related to the NF-κB pathway in ALI published between 2005 and 2024 was systematically retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using CiteSpace, VOSviewer, and the bibliometrix R package to comprehensively analyze publication trends, countries and institutions, authors and journals, most impactful articles, and keyword co-occurrence in this field. In addition, a mechanistic review was integrated to summarize the cell type-specific roles of the NF-κB pathway in macrophages, epithelial cells, and endothelial cells. RESULTS: A total of 916 articles were included, authored by 4,446 individuals and affiliated with 984 institutions and 302 journals, distributed across 46 countries and regions. The most prolific author, institution, country, and journal were Ware LB, Jilin University, China, and International Immunopharmacology, respectively. Highly cited analysis indicated that the most influential research focused primarily on NF-κB-mediated intercellular interactions, cell death, and drug modulation. High-frequency terms including ALI, NF-κB pathway, inflammation, oxidative stress, and apoptosis were identified, indicating core research hotspots in the field. Cluster and temporal analyses further highlight Toll-like receptor 4 (TLR4) signaling, endothelial and macrophage regulation, barrier dysfunction, and NF-κB targeted interventions as key and evolving research themes in ALI. From a cellular perspective, the NF-κB pathway regulates macrophage polarization and the barrier integrity of pulmonary endothelial and epithelial cells. CONCLUSIONS: This study demonstrates that research on the NF-κB pathway in ALI has received increasing attention over the past two decades. Our results indicate that future research should focus on time- and cell-specific therapeutic strategies to modulate the NF-κB pathway, thereby optimizing the treatment of ALI.