An article "CD146(+) cells are essential for kidney vasculature development" by Seppo Vainio group

 Kidney Int. 2016 Apr 18. pii: S0085-2538(16)00378-1. doi: 10.1016/j.kint.2016.02.021. [Epub ahead of print]

CD146(+) cells are essential for kidney vasculature development

Halt KJ(1), Pärssinen HE(1), Junttila SM(1), Saarela U(1), Sims-Lucas S(2), Koivunen P(3), Myllyharju J(1), Quaggin S(4), Skovorodkin IN(1), Vainio SJ(5).

Author information:  (1)Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, Oulu, Finland; Center of Excellence in Cell-Extracellular Matrix Research, Oulu, Finland. (2)Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. (3)Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, Oulu, Finland. (4)Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, Oulu, Finland; Division of Nephrology and Hypertension, Feinberg School of  Medicine, Northwestern University, Chicago, IL, USA. (5)Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; Biocenter Oulu, Oulu,  Finland; Center of Excellence in Cell-Extracellular Matrix Research, Oulu, Finland; InfoTech Oulu, Oulu, Finland. Electronic address: Seppo.Vainio@oulu.fi.

The kidney vasculature is critical for renal function, but its developmental assembly mechanisms remain poorly understood and models for studying its assembly dynamics are limited. Here, we tested whether the embryonic kidney contains endothelial cells (ECs) that are heterogeneous with respect to VEGFR2/Flk1/KDR, CD31/PECAM, and CD146/MCAM markers. Tie1Cre;R26R(YFP)-based fate mapping with a time-lapse in embryonic kidney organ culture successfully depicted the dynamics of kidney vasculature development and the correlation of the process with the CD31(+) EC network. Depletion of Tie1(+) or CD31(+) ECs from embryonic kidneys, with either Tie1Cre-induced diphtheria toxin susceptibility or cell surface marker-based sorting in a novel dissociation and reaggregation technology, illustrated substantial EC network regeneration. Depletion of the CD146(+) cells  abolished this EC regeneration. Fate mapping of green fluorescent protein (GFP)-marked CD146(+)/CD31(-) cells indicated that they became CD31(+) cells, which took part in EC structures with CD31(+) wild-type ECs. EC network development depends on VEGF signaling, and VEGF and erythropoietin are expressed  in the embryonic kidney even in the absence of any external hypoxic stimulus. Thus, the ex vivo embryonic kidney culture models adopted here provided novel ways for targeting renal EC development and demonstrated that CD146(+) cells are  critical for kidney vasculature development.

 

Viimeksi päivitetty: 17.5.2016