Der Einfluss des Biokomplexes RiV auf humane venöse Endothelzellen

Der Biokomplex “Reaktionsmuster in Vertebratenzellen” (RiV) besteht aus elektronenmikroskopisch nachweisbaren Partikeln, die stressinduziert sezerniert werden. Der Transkriptionsfaktor NF-kappa B ist bei inflammatorischen Prozessen und insbesondere auch bei der endothelialen Dysfunktion von Bedeutung. Ich habe die Hypothese untersucht, dass RiV-Partikel die zytokin-induzierte Expression von zellulären Adhäsionsmolekülen (ICAM-1, VCAM-1, E-Selektin) und des „Lectin-like oxidized“-LDL-Rezeptors-1 (LOX-1) in humanen umbilikalen venösen Endothelzellen (HUVEC) reduziert. Nach einer Inkubationszeit von vier Stunden wurde die TNF-alpha-induzierte mRNA-Expression von ICAM-1, VCAM-1 und LOX-1 unter dem Einfluss von RiV über eine reduzierte Translokation von NF-kappa B signifikant vermindert. Nach einer Inkubationszeit von 16 Stunden zeigte sich eine gesteigerte mRNA-Expression bei Exposition mit RiV durch eine Neusynthese der mRNA im Vergleich zu TNF-alpha-behandelten Endothelzellen. Die Oberflächenexpression blieb unverändert. Unter dem Einfluss von RiV auf TNF-alpha-stimulierte HUVEC wurde das Shedding von sICAM-1 und sE-Selektin induziert. RiV hatte keinen relevanten Einfluss auf die Expression der endothelialen NO-Synthase, eNOS. Der Biokomplex RiV enthält thermosensitive und thermostabile Komponenten.The bio-complex „reaction pattern in vertebrate cells“ (RiV) is mainly represented by characteristic exosome-like particles – as a reaction product of cells to specific stress. The transcription factor NF-kappa B plays a central role in inflammation and also in endothelial dysfunction. I tested the hypothesis that a RiV particle preparation reduces cytokine-induced expression of cellular adhesion molecules (ICAM-1, VCAM-1, E-selectin) and of lectin-like oxidized LDL-receptor-1, LOX-1, in human umbilical vein endothelial cells (HUVEC). Pre-incubation of HUVEC with RiV before stimulation with TNF-alpha reduced ICAM-1, VCAM-1 and LOX-1 mRNA-expression significantly after fours hours by attenuation of NF-kappa B translocation compared to TNF-alpha-treated cells. After 16 hours, pre-incubation of HUVEC with RiV increased mRNA expression of the molecules by de novo-synthesis compared to TNF-alpha-treated cells. No significant effects on surface expression were observed. Shedding of sICAM-1 and sE-selectin was induced after 16 hours co-incubation of TNF-alpha-treated cells with RiV. There were no relevant effects on expression of endothelial NO synthase, eNOS. The bio-complex RiV consist of thermosensitive and thermostable components

Kidney Cancer and Chronic Kidney Disease: Too Close for Comfort

Kidney cancer and chronic kidney disease are two renal pathologies with very different clinical management strategies and therapeutical options. Nonetheless, the cellular and molecular mechanisms underlying both conditions are closely related. Renal physiology is adapted to operate with a limited oxygen supply, making the kidney remarkably equipped to respond to hypoxia. This tightly regulated response mechanism is at the heart of kidney cancer, leading to the onset of malignant cellular phenotypes. Although elusive, the role of hypoxia in chronic kidney diseases is emerging as related to fibrosis, a pivotal factor in decaying renal function. The present review offers a perspective on the common biological traits shared between kidney cancer and chronic kidney disease and the available and prospective therapies for both conditions