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

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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.

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Acknowledgments

The authors thank Karin Pettersson and Sofia Wittgren for their excellent technical assistance. They also thank Dr. Colin Niaudet for critical discussion and material supply.

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Author notes

  1. Carolina E. Hagberg

    Present address: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

Authors and Affiliations

  1. Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Scheeles Väg 2, A3:P4, 17177, Stockholm, Sweden

    Lars Muhl, Christine Moessinger, Milena Z. Adzemovic, Ingrid Nilsson, Manuel Zeitelhofer, Carolina E. Hagberg, Annelie Falkevall & Ulf Eriksson

  2. Department Biotechnology and Molecular Medicine, A.I.V. Institute for Molecular Science, University of Eastern Finland, Kuopio, Finland

    Marike H. Dijkstra, Jenni Huusko & Seppo Ylä-Herttuala

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  1. Lars Muhl
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  2. Christine Moessinger
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  3. Milena Z. Adzemovic
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Correspondence to Ulf Eriksson.

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Conflict of interest

L.M., C.M., I.N., M.Z., A.F. and U.E. are shareholders in a company within the diabetes field. This does not alter the authors’ adherence to all policies of the Cell and Tissue Research journal. All authors declare that no other competing interest exists.

Additional information

This study was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, Karolinska Institutet and CSL (Melbourne, Australia). L.M. was supported by the Swedish Society for Medical Research (SSMF). C.M. held an EMBO Longterm Fellowship co-funded by the European Commission (EMBOCOFUND2010, GA-210-267146) with support from Marie Curie Actions. C.E.H. is supported by the Swedish Research Council, the Swedish Society for Medical Research (SSMF) and the Wilhelm och Else Stockmanns Stiftelse.

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Muhl, L., Moessinger, C., Adzemovic, M.Z. et al. Expression of vascular endothelial growth factor (VEGF)-B and its receptor (VEGFR1) in murine heart, lung and kidney. Cell Tissue Res 365, 51–63 (2016). https://doi.org/10.1007/s00441-016-2377-y

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