Bradykinin-bradykinin receptor (B1R) signalling is involved in the blood-brain barrier disruption in moyamoya disease.

Autor: Wang H; Department of Pharmacy, The Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People's Hospital of Lianyungang/First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, China., Sun W; Translational Pharmaceutical Laboratory, Jining First People's Hospital, Shandong First Medical University, Jining, China.; Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, China., Li F; Department of neurosurgery, Tengzhou Central People's Hospital, Jining Medical University, Tengzhou, China., Jiang P; Translational Pharmaceutical Laboratory, Jining First People's Hospital, Shandong First Medical University, Jining, China.; Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, China., Wang L; Translational Pharmaceutical Laboratory, Jining First People's Hospital, Shandong First Medical University, Jining, China.; Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, China., Zhou N; Translational Pharmaceutical Laboratory, Jining First People's Hospital, Shandong First Medical University, Jining, China.; Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, China., Feng L; Department of Neurosurgery, Jining First People's Hospital, Shandong First Medical University, Jining, China.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2023 Dec; Vol. 27 (24), pp. 4069-4079. Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1111/jcmm.17989
Abstrakt: Moyamoya disease (MMD) is a rare disorder of the cerebrovascular system. It is a steno-occlusive disease that involves angiogenesis and blood-brain barrier (BBB) disruption. Bradykinin (BK), its metabolite des-Arg9-BK, and receptor (B1R) affect angiogenesis and BBB integrity. In this study, we aimed to investigate the changes in BK, B1R and des-Arg9-BK levels in the serum and brain tissues of patients with MMD and explore the underlying mechanism of these markers in MMD. We obtained the serum samples and superficial temporal artery (STA) tissue of patients with MMD from the Department of Neurosurgery of the Jining First People's Hospital. First, we measured BK, des-Arg9-BK and B1R levels in the serum of patients by means of ELISA. Next, we performed immunofluorescence to determine B1R expression in STA tissues. Finally, we determined the underlying mechanism through Western blot, angiogenesis assay, immunofluorescence, transendothelial electrical resistance and transcytosis assays. Our results demonstrated a significant increase in the BK, des-Arg9-BK and B1R levels in the serum of patients with MMD compared to healthy controls. Furthermore, an increase in the B1R expression level was observed in the STA tissues of patients with MMD. BK and des-Arg9-BK could promote the migratory and proliferative abilities of bEnd.3 cells and inhibited the formation of bEnd.3 cell tubes. In vitro BBB model showed that BK and des-Arg9-BK could reduce claudin-5, ZO-1 and occluding expression and BBB disruption. To the best of our knowledge, our results show an increase in BK and B1R levels in the serum and STA tissues of patients with MMD. BK and Des-Arg9-BK could inhibit angiogenesis, promote migratory and proliferative capacities of cells, and disrupt BBB integrity. Therefore, regulating BK, des-Arg9-BK and B1R levels in the serum and the brain could be potential strategies for treating patients with MMD.
(© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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