Cell and Tissue Research

, Volume 365, Issue 1, pp 51–63 | Cite as

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

  • Lars Muhl
  • Christine Moessinger
  • Milena Z. Adzemovic
  • Marike H. Dijkstra
  • Ingrid Nilsson
  • Manuel Zeitelhofer
  • Carolina E. Hagberg
  • Jenni Huusko
  • Annelie Falkevall
  • Seppo Ylä-Herttuala
  • Ulf Eriksson
Regular Article

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.

Keywords

VEGF-B VEGFR1 Gene expression pattern Endothelial cells Insulin sensitivity 

Notes

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.

Compliance with ethical standards

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.

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Lars Muhl
    • 1
  • Christine Moessinger
    • 1
  • Milena Z. Adzemovic
    • 1
  • Marike H. Dijkstra
    • 2
  • Ingrid Nilsson
    • 1
  • Manuel Zeitelhofer
    • 1
  • Carolina E. Hagberg
    • 1
    • 3
  • Jenni Huusko
    • 2
  • Annelie Falkevall
    • 1
  • Seppo Ylä-Herttuala
    • 2
  • Ulf Eriksson
    • 1
  1. 1.Department of Medical Biochemistry and Biophysics, Division of Vascular BiologyKarolinska InstitutetStockholmSweden
  2. 2.Department Biotechnology and Molecular Medicine, A.I.V. Institute for Molecular ScienceUniversity of Eastern FinlandKuopioFinland
  3. 3.Department of Cell and Molecular BiologyKarolinska InstitutetStockholmSweden

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