Functional convergence of Akt protein with VEGFR-1 in human endothelial progenitor cells exposed to sera from patient with type 2 diabetes mellitus
Küçük Resim Yok
Tarih
2017
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Academic Press Inc Elsevier Science
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Diabetes mellitus type 2 predisposes patients to various microvascular complications. In the current experiment, the potent role of diabetes mellitus was investigated on the content of VEGFR-1,-2, Tie-1 and-2, and Akt in human endothelial progenitor cells. The gene expression profile of mTOR and Hedgehog signaling pathways were measured by PCR array. The possible crosstalk between RTKs, mTOR and Hedgehog signaling was also studied by bioinformatic analysis. Endothelial progenitor cells were incubated with serum from normal and diabetic for 7 days. Compared to non treated cells, diabetic serum-induced cell apoptosis (similar to 2-fold) and prohibited cell migration toward bFGF (p < 0.001). EUSA analysis showed that diabetes exposed cells had increased abundance of Tie-1,-2 and VEGFR-2 and reduced amount of VEGFR-1 (p < 0.0001) in diabetic cells. Western blotting showecIA marked reduction in the protein level of Akt after cells exposure to serum from diabetic subjects (p < 0.0001). PCR array revealed a significant stimulation of both mTOR and Hedgehog signaling pathways in diabetic cells (p < 0.05). According to data from bioinformatic datasets, we showed VEGFR-1,-2 and Tie-2, but not Tie-1, are master regulators of angiogenesis. There is a crosstalk between RTK5 and mTOR signaling by involving P62, GABARAPLI, and HTT genes. It seems that physical interaction and co-expression of Akt decreased the level of VEGFR-1 in diabetic cells. Regarding data from the present experiment, diabetic serum contributed to uncontrolled induction of both mTOR and Hedgehog signaling in endothelial progenitor cells. Diabetes mellitus induces mTOR pathway by involving receptor tyrosine kinases while Hedgehog stimulation is independent of these receptors. (C) 2017 Elsevier Inc. All rights reserved.
Açıklama
Anahtar Kelimeler
Human endothelial progenitor cells, Diabetes mellitus, Receptor tyrosine kinases, mTOR and Hedgehog signaling pathways
Kaynak
Microvascular Research
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
114
