Bdkrb1, encoding the bradykinin B1 receptor, is involved in the kallikrein-kinin system. Bradykinin, by activating BDKRB1/B2, can prompt calcium influx. BDKRB1 is associated with multiple biological pathways such as the Ca2+-MEK1-ERK1/2-NF-κB pathway, and is important in inflammation, cell migration, and tissue remodeling [1,4,5,6]. Genetic models, like knockout mice, are valuable for studying its functions.

In glioblastoma cells, knocking-down BDKRB1 decreased aquaporin 4 (AQP4) mRNA expression and cell migration and invasion, indicating BDKRB1's role in promoting glioblastoma cell migration and invasion through regulating AQP4 expression via the Ca2+-MEK1-ERK1/2-NF-κB mechanism [1]. In Wolfram syndrome rat models, Bdkrb1 expression was drastically down-regulated at an early stage, suggesting its disturbance in the normal functioning of the renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) [2]. Mice lacking Cd13 or Bdkrb1 were resistant to bleomycin-induced skin fibrosis and inflammation, highlighting BDKRB1's role in scleroderma fibrosis [3]. In a neuropathic pain model, an antagonist of BDKRB1 suppressed the over-expressed BDKRB1 levels and inhibited hyperpathia, while remimazolam alleviated neuropathic pain by inactivating BDKRB1 signalling [5]. In experimental autoimmune encephalomyelitis, Bdkrb1-deficient mice showed more severe disease with enhanced CNS-immune cell infiltration, suggesting Bdkrb1 limits encephalitogenic T lymphocyte recruitment to the CNS [6]. Kinin B1 receptor knockout mice had increased bone loss and more osteoclasts in a periodontitis model, indicating Bdkrb1's role in periodontitis pathogenesis [7].

In conclusion, Bdkrb1 plays essential roles in multiple biological processes and disease conditions. Model-based research, especially KO mouse models, has revealed its functions in cancer cell migration, neurodegenerative diseases, fibrosis, neuropathic pain, CNS inflammation, and periodontitis, providing potential therapeutic targets for these diseases.