ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-OR135

Soluble Nogo-B Overexpression Ameliorates Diabetic Glomerulopathy

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental


  • Hernandez, Ivan, King's College London, London, United Kingdom
  • Ricciardi, Carlo alberto, King's College London, London, United Kingdom
  • White, Kathryn E., Newcastle University, Newcastle upon Tyne, United Kingdom
  • Hayward, Anthea Elaine, King's College London, London, United Kingdom
  • Bai, Xiaoyan, Nanfang Hospital, Southern Medical University, Guangzhou, China
  • Hou, Fan Fan, Nanfang Hospital, Southern Medical University, Guangzhou, China
  • Long, David A., University College London, London, United Kingdom
  • Gnudi, Luigi, King's College London, London, United Kingdom

Diabetic glomerulopathy (DG) is characterized by altered vascular remodelling, increased vascular permeability. Neurite Outgrowth Inhibitor (Nogo)-B and its soluble form (sNogo-B) bind to NgBR and have been implicated in vascular remodelling. Full-length Nogo-B is expressed in glomerular endothelial cells and podocytes and is downregulated in experimental model of diabetic nephropathy and in patients with diabetic nephropathy (DN). Our aims were to investigate whether overexpression of sNogo-B could ameliorate DG in an experimental animal model of diabetes.


8-10 weeks-old male DBA/2J mice were made diabetic (streptozotocin), and administered (12-14 week-old) an adeno-associated viral vector (AAV) expressing sNogoB or GFP (control). Animals were divided into four groups: non-diabetic (ND) and diabetic (D) mice treated with either GFP-AAV or sNogo-B-AAV followed by 12-14 weeks of diabetes. Blood pressure was assessed with tail-cuff methodology, plasma sNogo-B levels by ELISA, full-length Nogo-B and AKT phosphorylation with immunoblotting, creatinine by mass spectrometry, albuminuria by fluorescence, and glomerular ultrastructure by electron microscopy.


sNogo-B-AAV allowed a sustained expression of sNogoB in the circulation (p<0.05). Diabetes-mediated albuminuria (p<0.01) was ameliorated by sNogo-B upregulation (p=0.04). Similarly, increase in creatinine clearance was corrected by sNogo-B overexpression to control ND mice levels (P<0.006). Blood pressure was similar in all groups. sNogo-B overexpression ameliorated diabetes-mediated mesangial expansion (p<0.05), full-length Nogo-B downregulation (p=0.02), and blunted Akt-Serine phosphorylation (p=0.01) in diabetic mice in kidney cortex lysate.


Overexpression of sNogo-B ameliorates DG via prevention of diabetes-mediated Nogo-B downregulation. Ongoing work is dissecting the major molecular mechanisms involved. sNogo-B could represent a potential novel future treatment for DG.