MO630SNOGO-B IS AN IMPORTANT CONTRIBUTOR TO GLOMERULAR ENDOTHELIAL CELL STABILITY AND VASCULAR REMODELLING INTERVENING ON VEGFA/VEGFR2 SIGNALLING
| Autor: | Luigi Gnudi, Carlo Alberto Ricciardi, David Long |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Nephrology Dialysis Transplantation. 36 |
| ISSN: | 1460-2385 0931-0509 |
| Popis: | Background and Aims Nogo-B is an endoplasmic reticulum protein present as a full length and circulating soluble isoform (sNogo-B) corresponding to the first ∼200aa of the N-terminus. Nogo-B is expressed in glomerular endothelial cells (GECs) and is downregulated in the diabetic glomeruli; its repletion, ameliorates diabetic glomerulopathy. However, the precise biological role of Nogo-B and its soluble form in GEC is not well understood. We hypothesise that sNogo-B could modulate VEGFA/VEGFR2 signalling, and vascular remodelling resulting in improved GECs health and vascular remodelling (vessel repair/new vessel formation). We predict that this effect may be mediated by changes in VEGFA/VEGFR2 signalling; a critical signalling pathway which regulates blood vessel function in physiology and disease. Method For this experiment we used human conditionally immortalised GECs. Cells were used after differentiation at 37°. GECs were infected with adenovirus vector expressing sNogo-B or identical vector lacking sNogo-B cDNA (control vector). Cells were serum starved (4 hours, FBS 2%) and exposed to VEGFA (50 ng/ml) for 5’ 10’ 15’ min and VEGFR2 phosphorylation assessed with western immunoblotting. Results VEGFA-Mediated VEGFR2 phosphorylation was upregulated in wild-type GECs after 15 min VEGFA incubation (P Conclusion sNogo-B prevents the VEGFA mediated VEGFR2 phosphorylation in GECs. Upregulation of VEGFA/VEGFR2 signalling has been implicated in diabetic glomerulopathy. sNogo-B inhibition of VEGFA/VEGFR2 signalling opens new investigations looking at the potential role of sNogo-B as therapeutic target in diabetic nephropathy. |
| Databáze: | OpenAIRE |
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