Wang Li, Tan Rui-Zhi, Chen Yue, Wang Hong-Lian, Liu Yu-Hang, Wen Dan, Fan Jun-Ming
a Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital , Sichuan Medical University , Luzhou , Sichuan , China ;
b Department of Nephrology , The First People's Hospital of Zigong , Zigong , Sichuan , China ;
Ren Fail. 2016;38(3):458-64. doi: 10.3109/0886022X.2016.1138831. Epub 2016 Feb 2.
Cytotoxin-associated antigen A (CagA), a major virulence factor of Helicobacter pylori (Hp), is associated with the pathogenesis of peptic ulcer and gastric cancer. Recent researches demonstrated that Hp exists in palatine tonsil in all studied IgA nephropathy (IgAN) patients, most of which were CagA-positive, suggesting that CagA may be a causative pathogenic factor of IgAN. However, the underlying molecular mechanisms and signaling pathway are still largely unclear. In the present study, CCK8 assay, enzyme-linked immunosorbent assay, and immunohistochemistry were performed to investigate the effect of CagA on cell proliferation and extracellular matrix secretion in rat glomerular mesangial cells. RT-PCR and western blotting were used to reveal the potential signaling pathway. Rat glomerular mesangial cells were treated with recombinant CagA protein for 72 h, in a dose- and time-dependent manner. We found that CagA promoted cell proliferation and extracellular matrix secretion by inhibiting signaling pathway of apoptosis. Taken together, these findings suggested that CagA induced cellular injury in glomerular mesangium by proliferation and secretion of extracellular matrix, and may play an important role in pathogenesis of IgAN.
细胞毒素相关抗原A（CagA）是幽门螺杆菌（Hp）的一种主要毒力因子，与消化性溃疡和胃癌的发病机制有关。最近的研究表明，在所有研究的IgA肾病（IgAN）患者的腭扁桃体中均存在Hp，其中大多数为CagA阳性，这表明CagA可能是IgAN的致病因素。然而，其潜在的分子机制和信号通路仍 largely不清楚。在本研究中，进行了CCK8检测、酶联免疫吸附测定和免疫组织化学，以研究CagA对大鼠肾小球系膜细胞增殖和细胞外基质分泌的影响。采用RT-PCR和蛋白质印迹法揭示潜在的信号通路。用重组CagA蛋白处理大鼠肾小球系膜细胞72小时，呈剂量和时间依赖性。我们发现CagA通过抑制凋亡信号通路促进细胞增殖和细胞外基质分泌。综上所述，这些发现表明CagA通过细胞增殖和细胞外基质分泌诱导肾小球系膜细胞损伤，并可能在IgAN的发病机制中起重要作用。
