Blood–brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins

Scientific Reports

GOING-FWD Collaborators¹  Agne Laucyte-Cibulskiene²  Peter Barany²  Peter Stenvinkel²  Olof Heimbürger²  Leah Hernandez²  Karolina Kublickiene²  Samsul Arefin²  Liam J. Ward²  Thomas Ebert²  Lars Wennberg³ 

[1] ;Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Renal Medicine, Karolinska Institutet;Department of Transplantation Surgery, Karolinska University Hospital;

DOI  :  10.1038/s41598-022-08387-7

来源: DOAJ

【 摘 要 】

Abstract Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood–brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.

【 授权许可】

Unknown