Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina
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Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. / Qiu, Yi; Zhao, Di; Butenschön, Vicki-Marie; Bauer, Alexander T; Schneider, Stefan W; Skolnik, Edward Y; Hammes, Hans-Peter; Wieland, Thomas; Feng, Yuxi.
in: ACTA DIABETOL, Jahrgang 53, Nr. 1, 02.2016, S. 81-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina
AU - Qiu, Yi
AU - Zhao, Di
AU - Butenschön, Vicki-Marie
AU - Bauer, Alexander T
AU - Schneider, Stefan W
AU - Skolnik, Edward Y
AU - Hammes, Hans-Peter
AU - Wieland, Thomas
AU - Feng, Yuxi
PY - 2016/2
Y1 - 2016/2
N2 - AIMS: Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. It might therefore supply UTP for the formation of UDP-GlcNAc from glucose. As NDPKB contributes to vascular dysfunction, we speculate that NDPKB might play a role in microangiopathies, such as diabetic retinopathy (DR). Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms.METHODS: Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose.RESULTS: Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. Hyperglycemia further aggravates pericyte loss in diabetic NDPKB(-/-) retinas. AC formation was detected in the diabetic NDPKB(-/-) retinas. Similar to hyperglycemia, NDPKB deficiency induced Ang2 expression and protein GlcNAcylation that were not further altered in the diabetic retinas. In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation.CONCLUSIONS: Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage.
AB - AIMS: Nucleoside diphosphate kinase B (NDPKB) is capable of maintaining the cellular nucleotide triphosphate pools. It might therefore supply UTP for the formation of UDP-GlcNAc from glucose. As NDPKB contributes to vascular dysfunction, we speculate that NDPKB might play a role in microangiopathies, such as diabetic retinopathy (DR). Therefore, we investigated the impact of NDPKB on retinal vascular damage using NDPKB(-/-) mice during development of DR and its possible mechanisms.METHODS: Pericyte loss and acellular capillary (AC) formation were assessed in streptozotocin-induced diabetic NDPKB(-/-) and wild-type (WT) mice. Expression of angiopoietin-2 (Ang2) and protein N-acetylglucosamine modification (GlcNAcylation) were assessed by western blot and/or immunofluorescence in the diabetic retinas as well as in endothelial cells depleted of NDPKB by siRNA and stimulated with high glucose.RESULTS: Similar to diabetic WT retinas, non-diabetic NDPKB(-/-) retinas showed a significant decrease in pericyte coverage in comparison with non-diabetic WT retinas. Hyperglycemia further aggravates pericyte loss in diabetic NDPKB(-/-) retinas. AC formation was detected in the diabetic NDPKB(-/-) retinas. Similar to hyperglycemia, NDPKB deficiency induced Ang2 expression and protein GlcNAcylation that were not further altered in the diabetic retinas. In cultured endothelial cells, stimulation with high glucose and NDPKB depletion comparably increased Ang2 expression and protein GlcNAcylation.CONCLUSIONS: Our data identify NDPKB as a protective factor in the retina, which controls Ang2 expression and the hexosamine pathway. NDPKB-deficient mice are a suitable model for studying mechanisms underlying diabetic retinal vascular damage.
KW - Angiopoietin-2
KW - Animals
KW - Cells, Cultured
KW - Diabetes Mellitus, Experimental
KW - Diabetic Retinopathy
KW - Endothelial Cells
KW - Glucose
KW - Hexosamines
KW - Human Umbilical Vein Endothelial Cells
KW - Humans
KW - Hyperglycemia
KW - Male
KW - Mice
KW - Mice, Knockout
KW - NM23 Nucleoside Diphosphate Kinases
KW - Pericytes
KW - Retina
KW - Retinal Vessels
KW - Up-Regulation
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1007/s00592-015-0752-x
DO - 10.1007/s00592-015-0752-x
M3 - SCORING: Journal article
C2 - 25900369
VL - 53
SP - 81
EP - 89
JO - ACTA DIABETOL
JF - ACTA DIABETOL
SN - 0940-5429
IS - 1
ER -
