WFRF:(Stenvinkel Peter)
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Blood-brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins
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- Hernandez, Leah (författare)
- Karolinska Institutet,Karolinska Institute
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- Ward, Liam J. (författare)
- Karolinska Institute
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- Arefin, Samsul (författare)
- Karolinska Institutet,Karolinska Institute
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- (creator_code:org_t)
- 2022-03-15
- 2022
- Engelska.
- Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
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- Hernandez, Leah
- Ward, Liam J.
- Arefin, Samsul
- Ebert, Thomas
- Laucyte-Cibulski ...
- Heimbürger, Olof
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- Barany, Peter
- Wennberg, Lars
- Stenvinkel, Pete ...
- Kublickiene, Kar ...
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