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| Content Provider | Springer Nature Link |
|---|---|
| Author | Muhl, Lars Moessinger, Christine Adzemovic, Milena Z. Dijkstra, Marike H. Nilsson, Ingrid Zeitelhofer, Manuel Hagberg, Carolina E. Huusko, Jenni Falkevall, Annelie Ylä Herttuala, Seppo Eriksson, Ulf |
| Copyright Year | 2016 |
| 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. |
| Starting Page | 51 |
| Ending Page | 63 |
| Page Count | 13 |
| File Format | |
| ISSN | 0302766X |
| Journal | Cell and Tissue Research |
| Volume Number | 365 |
| Issue Number | 1 |
| e-ISSN | 14320878 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2016-03-01 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | VEGF-B VEGFR1 Gene expression pattern Endothelial cells Insulin sensitivity Human Genetics Proteomics Molecular Medicine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Histology Pathology and Forensic Medicine |
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