Expression of vascular endothelial growth factor (VEGF)-B and its receptor (VEGFR1) in murine heart, lung and kidney

Abstract

Metabolic diseases, such as obesity and diabetes, are a serious burden for the health system. Vascular endothelial growth factor (VEGF)-B has been shown to regulate tissue uptake and accumulation of fatty acids and is thus involved in these metabolic diseases. However, the cell-type-specific expression pattern of Vegfb and its receptor (VEGFR1, gene Flt1) remains unclear. We explore the expression of Vegfb and Flt1 in the murine heart, lung and kidney by utilizing β-galactosidase knock-in mouse models and combining the analysis of reporter gene expression and immunofluorescence microscopy. Furthermore, Flt1 heterozygous mice were analyzed with regard to muscular fatty acid accumulation and peripheral insulin sensitivity. Throughout the heart, Vegfb expression was found in cardiomyocytes with a postnatal ventricular shift corresponding to known changes in energy requirements. Vegfb expression was also found in the pulmonary myocardium of the lung and in renal epithelial cells of the thick ascending limb of Henle's loop, the connecting tubule and the collecting duct. In all analyzed organs, VEGFR1 expression was restricted to endothelial cells. We also show that reduced expression of VEGFR1 resulted in decreased cardiac fatty acid accumulation and increased peripheral insulin sensitivity, possibly as a result of attenuated VEGF-B/VEGFR1 signaling. Our data therefore support a tightly controlled, paracrine signaling mechanism of VEGF-B to VEGFR1. The identified cell-specific expression pattern of Vegfb and Flt1 might form the basis for the development of cell-type-targeted research models and contributes to the understanding of the physiological and pathological role of VEGF-B/VEGFR1 signaling.

Insights into the Mechanisms Involved in Protective Effects of VEGF-B in Dopaminergic Neurons

“…In a study by Muhl et al the expression of both VEGF-B and VEGFR-1 was explored in the murine heart, lung, and kidney. In all organs, there was a cell-specific pattern with VEGFR-1 expression restricted to endothelial cells and VEGF-B expression was found in cardiomyocytes, pulmonary myocardium of the lung, and renal epithelial cells of the kidney [36]. During ischemic stroke, VEGF-B expression was increased in neurons and inflammatory (macrophage/microglial) cells of the ischemic border zone after cerebral artery occlusion in a rat model [37].…”

An update on diabetic kidney disease, oxidative stress and antioxidant agents

“…Therefore; hyperglycemia induces autoxidation of glucose and glycosylation of proteins by generation of free radicals thus, increases the reactive oxygen species (ROS) accompanied by a reduction in antioxidant activity which leads to the occurrence of oxidative stress. These can cause endothelial dysfunction, insulin resistance, and alterations in the proportion and functions of pancreatic 𝛽 cells and ultimately leads to diabetic microvascular and macrovascular complications (6,7). Based on evidence, ROS induces several cellular signaling cascades which in turn promote transcription of stress-related genes and development of diabetic complications including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-𝜅B), an activated nuclear transcription factor by an elevation in ROS.…”

The influence of neurotransplantation with different allogenic tissues on the course of the spasticity and chronic pain syndrome after experimental spinal cord injury

“…Стимуляція ангіогенезу у най-гострішому та ранньому періоді після травми може мати не лише позитивний метаботропний ефект, а й спричиняти репефузійне ураження [63,64] або формування значної кількості новоутворених судин з неповноцінною бар'єрною функцією, тобто, потен-ціювати подальший аутоімунний процес. З високою вірогідністю з матеріалів, що використовували у досліджені, концентрація основного ангіогенного фактору VEGF максимальна у тканині фетальної нирки, менша -зрілої нюхової цибулини, мінімальна -фетального мозочка [48,[65][66][67][68].…”