Tags

Type your tag names separated by a space and hit enter

Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina.
Acta Diabetol. 2016 Feb; 53(1):81-9.AD

Abstract

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.

Authors+Show Affiliations

Institute for Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mybachstr. 14, 68169, Mannheim, Germany.Institute for Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mybachstr. 14, 68169, Mannheim, Germany.Institute for Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mybachstr. 14, 68169, Mannheim, Germany.Division of Experimental Dermatology, Department of Dermatology, Venereology, and Allergology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.Division of Experimental Dermatology, Department of Dermatology, Venereology, and Allergology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.Division of Nephrology, New York University Langone Medical Center, 560 1st Ave, New York, NY, 10016, USA.5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.Institute for Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mybachstr. 14, 68169, Mannheim, Germany.Institute for Experimental and Clinical Pharmacology and Toxicology, Medical Faculty Mannheim, University of Heidelberg, Mybachstr. 14, 68169, Mannheim, Germany. yuxi.feng@medma.uni-heidelberg.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25900369

Citation

Qiu, Yi, et al. "Nucleoside Diphosphate Kinase B Deficiency Causes a Diabetes-like Vascular Pathology Via Up-regulation of Endothelial Angiopoietin-2 in the Retina." Acta Diabetologica, vol. 53, no. 1, 2016, pp. 81-9.
Qiu Y, Zhao D, Butenschön VM, et al. Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. Acta Diabetol. 2016;53(1):81-9.
Qiu, Y., Zhao, D., Butenschön, V. M., Bauer, A. T., Schneider, S. W., Skolnik, E. Y., Hammes, H. P., Wieland, T., & Feng, Y. (2016). Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. Acta Diabetologica, 53(1), 81-9. https://doi.org/10.1007/s00592-015-0752-x
Qiu Y, et al. Nucleoside Diphosphate Kinase B Deficiency Causes a Diabetes-like Vascular Pathology Via Up-regulation of Endothelial Angiopoietin-2 in the Retina. Acta Diabetol. 2016;53(1):81-9. PubMed PMID: 25900369.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2015/04/23/ PY - 2015/01/28/received PY - 2015/03/30/accepted PY - 2015/4/23/entrez PY - 2015/4/23/pubmed PY - 2016/12/15/medline KW - Angiopoietin 2 KW - Diabetic retinopathy KW - Nucleoside diphosphate kinase B KW - O-linked acetylglucosamine KW - Retina SP - 81 EP - 9 JF - Acta diabetologica JO - Acta Diabetol VL - 53 IS - 1 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. SN - 1432-5233 UR - https://www.unboundmedicine.com/medline/citation/25900369/Nucleoside_diphosphate_kinase_B_deficiency_causes_a_diabetes_like_vascular_pathology_via_up_regulation_of_endothelial_angiopoietin_2_in_the_retina_ L2 - https://dx.doi.org/10.1007/s00592-015-0752-x DB - PRIME DP - Unbound Medicine ER -