Kim Junhyung, Lee Ji-Hye, Jang Si-Hyong, Lee Eun Young, Lee Mihye, Park Samel, Moon Jong-Seok
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan, 31151, Chungcheongnam-do, South Korea.
Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan, 31151, Chungcheongnam-do, South Korea.
Free Radic Biol Med. 2024 Nov 20;225:711-725. doi: 10.1016/j.freeradbiomed.2024.10.313. Epub 2024 Oct 31.
Mesangial expansion and proliferation have been implicated in the pathogenesis of IgA nephropathy (IgAN). Mesangial cells in glomerulus are important contributors to commencement of IgAN. From minimal mesangial expansion to diffuse proliferation, the mesangial alteration is linked to clinical and pathological features of IgAN. Although selenium-binding protein 1 (SBP1) is associated with tissue injury, the roles of SBP1 in mesangial proliferation and inflammation in glomerulus during IgAN remains unclear. In the present study, we found that SBP1 gene levels were elevated in kidney tissues of patients with IgAN. Also, SBP1 protein levels were elevated in proliferative mesangial cells of glomerulus in kidney tissues from patients with IgAN. Urinary SBP1 protein levels were elevated in patients with IgAN. Elevated urinary SBP1 levels were positively correlated with segmental glomerulosclerosis of the Oxford classification related to mesangial proliferation in patients with IgAN. Over-expression of SBP1 induced cellular proliferation via mitochondrial respiration in human renal mesangial cells. Consistently, SBP1 knockdown and mitochondrial respiration inhibition suppressed cellular proliferation and induced mitochondrial oxidative stress in human renal mesangial cells. Furthermore, SBP1 induced pro-inflammatory phenotype by gene expression and production of pro-inflammatory cytokines and chemokines including IL-6, CXCL10, and CCL5 via NF-κB activation in human renal mesangial cells. These results suggest that SBP1 contributes to mesangial proliferation and inflammation via mitochondrial respiration during IgAN.
系膜扩张和增殖与IgA肾病（IgAN）的发病机制有关。肾小球系膜细胞是IgAN发病的重要因素。从轻微的系膜扩张到弥漫性增殖，系膜改变与IgAN的临床和病理特征相关。尽管硒结合蛋白1（SBP1）与组织损伤有关，但SBP1在IgAN期间肾小球系膜增殖和炎症中的作用仍不清楚。在本研究中，我们发现IgAN患者肾组织中SBP1基因水平升高。此外，IgAN患者肾组织肾小球增殖性系膜细胞中SBP1蛋白水平升高。IgAN患者尿SBP1蛋白水平升高。尿SBP1水平升高与IgAN患者牛津分类中与系膜增殖相关的节段性肾小球硬化呈正相关。SBP1的过表达通过人肾系膜细胞中的线粒体呼吸诱导细胞增殖。一致地，SBP1基因敲低和线粒体呼吸抑制抑制了人肾系膜细胞的细胞增殖并诱导了线粒体氧化应激。此外，SBP1通过激活人肾系膜细胞中的NF-κB，通过基因表达以及促炎细胞因子和趋化因子（包括IL-6、CXCL10和CCL5）的产生，诱导促炎表型。这些结果表明，在IgAN期间，SBP1通过线粒体呼吸促进系膜增殖和炎症。
