Nogo-B May Mediate the Glomerular Endothelial Cell Injury of Hypertensive Nephropathy by Enhancing the Inflammatory Phenotype

Background: Nogo-B is an endoplasmic reticulum resident protein, which is mostly expressed in vascularendothelial cells and smooth muscle cells. Previous studies have elucidated the relationship betweenhypertension and Nogo-B in endothelial cells, but whether Nogo-B is involved in glomerularendothelial cell injury in hypertensive nephropathy and its mechanism is not clear. Methods: The localization of Noao-B was proved by immunohistochemistry lHC) and immunofluorescence lFstaining in renal tissue of hypertensive patients, and the relationship between it and systolic bloodpressure (SBP) and UACR was analyzed. In animal experiments, lHC, IF, PAS, gRT-PCR andWestern blot were employed to prove the localization of Nogo-B and analyze the relationship betweenits expression level and the degree of renal injury in Ang ll-induced Nogo-B KO and control mice. inthe vitro, the level of Nogo-B in endothelial cells (Ea.hy926) was knocked down by small interferingRNA (siRNA), and the correlation between Nogo-B expression and cell phenotypes were explored. Results: Nogo-B is expressed in glomerular endothelial cells and increased in hypertensive nephropathy. lt ispositively correlated with the patients’ SBP and UACR, n animal experiments, the renal pathologicadamage of Noao-B KO mice treated with hypertension was mild. The level of Nogo-B in endothelialcells is up-regulated in hypertensive environment and inflammatory markers including TNF-a, lL-1Band lL-6 were up-regulated. Knockdown of Nogo-B by siRNA reduces the inflammatory phenotype ofendothelial cells in hypertensive environment. Conclusion: Nogo-B may mediate the glomerular endothelial cell injury of hypertensive nephropathy by enhancingthe inflammatory phenotype.