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

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)1841-1852
Number of pages12
JournalDiabetes
Volume68
Issue number9
Early online date19 Jun 2019
DOIs
Publication statusPublished - 1 Sep 2019

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© 2019 by the American Diabetes Association.

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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 remodelling 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, abnormal angiogenesis and protecting glomerular capillary structure. Systemic sNogo-B overexpression in diabetic mice also associates with dampening VEGF-A signalling and reducing eNOS, 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.

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