Abstract
|
Advanced Oxidation Protein Products Aggravate Inflammation of Henoch-Schönlein Purpura Nephritis Through the RAGE-NF-κB Pathway
by Fengfang Wei, Weinan Zheng, Yuanbin Xu, Meixue Chen, Lin Lin, Qinghuang Zeng, Hongrong Zhang
|
|
|
Background: Henoch-Schönlein purpura nephritis (HSPN) is the most serious complication of allergic purpura (HSP). Advanced oxidized protein products (AOPPs) are an important damage factor in chronic kidney disease, and its expression level is also closely related to the pathogenesis of HSP. However, the role of AOPPs in HSPN reminds unclear. In the present study, we aimed to investigate the expression of AOPPs and its mechanism of inducing inflammation during the pathogenesis of HSPN in children.
Methods: We collected 20 patients with HSPN and 20 age- and gender-matched healthy controls in our hospital. ELISA, western blot, and immunofluorescence technique were performed to verify the above aim.
Results: Results showed that, as compared with the control group, serum levels of AOPPs in the HSPN increased significantly (p < 0.05). Serum IL-1β, IL-6 and TNF-α levels in the HSPN were also significantly higher than in the control group (p < 0.05). Moreover, the results showed that there was a positive correlation between serum AOPPs and inflammatory factor TNF-α, IL-6 and IL-1β level in children with HSPN. AOPPs treatment was found to significantly increase expression of RAGE, and p-P65, while the IκB was obviously reduced. Immunofluorescence showed that AOPPs significantly induce P65 nuclear metastasis. We further demonstrated that FPS-ZM1 (a selective RAGE inhibitor) and/or BAY 11-7082 (a selective NF-κB signaling pathway inhibitor) inhibited AOPPs-induced inflammation in HBZY-1 through blocking RAGE-NF-κB signaling pathway.
Conclusions: Collectively, these results implicated that AOPPs may be related to the pathogenesis of HSPN, AOPPs might induce or aggravate inflammation of HSPN through regulating RAGE-NF-κB signaling pathway. Above all, it has important clinical guiding significance for the prognosis judgment of HSPN, and can also provide new therapeutic targets for the HSPN.
DOI: 10.7754/Clin.Lab.2025.250559
|