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Complications

Overexpression of Circulating Soluble Nogo-B Improves Diabetic Kidney Disease by Protecting the Vasculature

  1. Ivan Hernandez-Diaz1,
  2. Jiaqi Pan1,
  3. Carlo Alberto Ricciardi1,
  4. Xiaoyan Bai2,
  5. Jianting Ke1,
  6. Kathryn E. White3,
  7. Maria Flaquer1,
  8. Georgia E. Fouli1,
  9. Fulye Argunhan1,
  10. Anthea E. Hayward1,
  11. Fan Fan Hou2,
  12. Giovanni E. Mann1,
  13. Robert Q. Miao4,
  14. David A. Long5 and
  15. Luigi Gnudi1⇑
  1. 1School of Cardiovascular Medicine & Sciences, British Heart Foundation Centre of Research Excellence, King’s College London, London, U.K.
  2. 2Division of Nephrology, State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
  3. 3Electron Microscopy Unit, Newcastle University, Newcastle upon Tyne, U.K.
  4. 4Medical College of Wisconsin, Milwaukee, WI
  5. 5Developmental Biology and Cancer Programme, Great Ormond Street Institute of Child Health, University College London, London, U.K.
  1. Corresponding author: Luigi Gnudi, luigi.gnudi{at}kcl.ac.uk
  1. J.P. and C.A.R. contributed equally.

Diabetes 2019 Sep; 68(9): 1841-1852. https://doi.org/10.2337/db19-0157
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This article has a correction. Please see:

  • Erratum. Overexpression of Circulating Soluble Nogo-B Improves Diabetic Kidney Disease by Protecting the Vasculature. Diabetes 2019;68: - February 01, 2020

Abstract

Damage to the vasculature is the primary mechanism driving chronic diabetic microvascular complications such as diabetic nephropathy, which manifests as albuminuria. Therefore, treatments that protect the diabetic vasculature have significant therapeutic potential. Soluble neurite outgrowth inhibitor-B (sNogo-B) is a circulating N-terminus isoform of full-length Nogo-B, which plays a key role in vascular remodeling following injury. However, there is currently no information on the role of sNogo-B in the context of diabetic nephropathy. We demonstrate that overexpression of sNogo-B in the circulation ameliorates diabetic kidney disease by reducing albuminuria, hyperfiltration, and abnormal angiogenesis and protecting glomerular capillary structure. Systemic sNogo-B overexpression in diabetic mice also associates with dampening vascular endothelial growth factor-A signaling and reducing endothelial nitric oxide synthase, AKT, and GSK3β phosphorylation. Furthermore, sNogo-B prevented the impairment of tube formation, which occurred when human endothelial cells were exposed to sera from patients with diabetic kidney disease. Collectively, these studies provide the first evidence that sNogo-B protects the vasculature in diabetes and may represent a novel therapeutic target for diabetic vascular complications.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db19-0157/-/DC1.

  • J.K. is currently affiliated with the Department of Nephrology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Guangdong, People’s Republic of China.

  • Received February 15, 2019.
  • Accepted June 10, 2019.
  • © 2019 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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Overexpression of Circulating Soluble Nogo-B Improves Diabetic Kidney Disease by Protecting the Vasculature
Ivan Hernandez-Diaz, Jiaqi Pan, Carlo Alberto Ricciardi, Xiaoyan Bai, Jianting Ke, Kathryn E. White, Maria Flaquer, Georgia E. Fouli, Fulye Argunhan, Anthea E. Hayward, Fan Fan Hou, Giovanni E. Mann, Robert Q. Miao, David A. Long, Luigi Gnudi
Diabetes Sep 2019, 68 (9) 1841-1852; DOI: 10.2337/db19-0157

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Overexpression of Circulating Soluble Nogo-B Improves Diabetic Kidney Disease by Protecting the Vasculature
Ivan Hernandez-Diaz, Jiaqi Pan, Carlo Alberto Ricciardi, Xiaoyan Bai, Jianting Ke, Kathryn E. White, Maria Flaquer, Georgia E. Fouli, Fulye Argunhan, Anthea E. Hayward, Fan Fan Hou, Giovanni E. Mann, Robert Q. Miao, David A. Long, Luigi Gnudi
Diabetes Sep 2019, 68 (9) 1841-1852; DOI: 10.2337/db19-0157
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