CHANGES OF THE CONTENT OF DLL4 AND Jag-1 ANGIOGENESIS REGULATORS IN HUMAN DERMIS IN ONTOGENESIS

Abstract

The goal of this study was to examine the contents of Dll 4 and Jag-1 angiogenesis regulators in human dermis at different age periods. Dll4 and Jag-1 were demonstrated by indirect immunohistochemistry in skin sections of fetuses of 20-40 gestational weeks and in persons aged from birth to 85 years. Dll4 was studied in 150 skin samples of 72 females and 78 males, while Jag-1 was examined in 120 samples of 58 females and 62 males. It is found that the immunoreactivity was mainly expressed by the endothelial cells. Vessels, which gave a positive reaction to Dll4 and Jag-1, were found throughout the entire thickness of the dermis, both in fetuses, and people of all age groups. Expression of Dll4 in the vessels of dermal microvasculature was shown to increase from 20 weeks of gestation to 20 years. With the further age increase, the intensity of the reaction of blood vessels for Dll4 was decreased. Expression of Jag-1 in dermal microvessels was enhanced from 20 weeks of gestation to 85 years. The results are discussed in connection with the role of Dll4 and Jag-1 in angiogenesis in human dermis during ontogeny.

Keywords

Dll4 / Jag-1 / dermis / ontogeny aging / skin / angiogenesis / blood vessels / Dll4 / Jag-1

References

[1] Гунин А. Г., Петров В. В., Васильева О. В. и др. Кровеносные сосуды в дерме человека в процессе старения // Успехи геронтол. 2014. Т. 27, вып. 1. С. 54-61.

[2] Abbas O. L., Borman H., Terzi Y. K. et al. Inhibition of the Notch pathway promotes flap survival by inducing functional neoangiogenesis // Ann. Plast. Surg. 2015. Vol. 74. P. 534-540.

[3] Benedito R., Rocha S. F., Woeste M. et al. Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGFVEGFR2 signalling // Nature. 2012. Vol. 484, № 7392. P. 110- 114.

[4] Camelo S., Raoul W., Lavalette S. et al. Delta-like 4 inhibits choroidal neovascularization despite opposing effects on vascular endothelium and macrophages // Angiogenesis. 2012. Vol. 15. P. 609-622.

[5] D’Souza B., Meloty-Kapella L., Weinmaster G. Canonical and non-canonical Notch ligands // Curr. Top. Dev. Biol. 2010. Vol. 92. P. 73-129.

[6] Kume T. Ligand-dependent Notch signaling in vascular formation // Adv. Exp. Med. Biol. 2012. Vol. 727. P. 210-222.

[7] Lee J. H., Yoo J. H. Knockdown of moesin expression accelerates cellular senescence of human dermal microvascular endothelial cells // Yonsei. Med. J. 2010. Vol. 51. P. 438-447.

[8] Leslie J. D., Ariza-McNaughton L., Bermange A. L. et al. Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis // Development. 2007. Vol. 134, № 5. P. 839-844.

[9] Liu Z. J., Shirakawa T., Li Y. et al. Regulation of Notch 1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis // Mol. Cell Biol. 2003. Vol. 23. P. 14-25.

[10] Nikolakis G., Makrantonaki E., Zouboulis C. C. Skin mirrors human aging // Horm. Mol. Biol. Clin. Investig. 2013. Vol. 16, № 1. P. 13-28.

[11] Rizzardi A. E., Johnson A. T., Vogel R. I. et al. Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring // Diagn. Pathol. 2012. Vol. 7, № 42. P. 1-10.

[12] Sawane M., Kajiya K. Ultraviolet light-induced changes of lymphatic and blood vasculature in skin and their molecular mechanisms // Exp. Dermatol. 2012. Vol. 21, № l. P. 22-25.

[13] Thomas J., Baker K., Han J. et al. Interactions between VEGFR and Notch signaling pathways in endothelial and neural cells // Cell. Mol. Life Sci. 2013. Vol. 70. P. 1779-1792.

[14] Yan M., Plowman G. D. Delta-like 4/Nath signaling and its therapeutic implications // Clin. Cancer Res. 2007. Vol. 13, № 24. P. 7243-7246.

RIGHTS & PERMISSIONS

Eco-Vector