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Neuroglia 2018, 1(1), 280-291; https://doi.org/10.3390/neuroglia1010019

Mediation of FoxO1 in Activated Neuroglia Deficient for Nucleoside Diphosphate Kinase B during Vascular Degeneration

1
Experimental Pharmacology, European Center of Angioscience, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
2
5th Med, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
Y.Q. and H.H. share first authorship.
*
Author to whom correspondence should be addressed.
Received: 4 July 2018 / Revised: 18 August 2018 / Accepted: 3 September 2018 / Published: 7 September 2018
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Abstract

The pathogenesis of diabetic retinopathy is closely associated with the breakdown of the neurovascular unit including the glial cells. Deficiency of nucleoside diphosphate kinase B (NDPK-B) results in retinal vasoregression mimicking diabetic retinopathy. Increased retinal expression of Angiopoietin-2 (Ang-2) initiates vasoregression. In this study, Müller cell activation, glial Ang-2 expression, and the underlying mechanisms were investigated in streptozotocin-induced diabetic NDPK-B deficient (KO) retinas and Müller cells isolated from the NDPK-B KO retinas. Müller cells were activated and Ang-2 expression was predominantly increased in Müller cells in normoglycemic NDPK-B KO retinas, similar to diabetic wild type (WT) retinas. Diabetes induction in the NDPK-B KO mice did not further increase its activation. Additionally, cultured NDPK-B KO Müller cells were more activated and showed higher Ang-2 expression than WT cells. Müller cell activation and Ang-2 elevation were observed upon high glucose treatment in WT, but not in NDPK-B KO cells. Moreover, increased levels of the transcription factor forkhead box protein O1 (FoxO1) were detected in non-diabetic NDPK-B KO Müller cells. The siRNA-mediated knockdown of FoxO1 in NDPK-B deficient cells interfered with Ang-2 upregulation. These data suggest that FoxO1 mediates Ang-2 upregulation induced by NDPK-B deficiency in the Müller cells and thus contributes to the onset of retinal vascular degeneration. View Full-Text
Keywords: angiopoietin-2; FoxO1; NDPK-B; neuroglia angiopoietin-2; FoxO1; NDPK-B; neuroglia
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Qiu, Y.; Huang, H.; Chatterjee, A.; Teuma, L.D.; Baumann, F.S.; Hammes, H.-P.; Wieland, T.; Feng, Y. Mediation of FoxO1 in Activated Neuroglia Deficient for Nucleoside Diphosphate Kinase B during Vascular Degeneration. Neuroglia 2018, 1, 280-291.

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