Zheng Nuoyan, Wang Donxian, Ming Hongyan, Zhang Haiqing, Yu Xueqing
Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China.
Translational Medical Center, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China.
BMC Nephrol. 2015 May 15;16:72. doi: 10.1186/s12882-015-0064-y.
B cell activating factor belonging to the TNF family (BAFF) is vital for B cell survival, proliferation and activation. Evidence indicates that BAFF is systemically or locally increased in glomerulonephritis (e.g. lupus nephritis, IgA nephropathy). However, the effect of BAFF on human mesangial cells is not known.
The impact of BAFF on the proliferation of a human mesangial cell line in vitro was investigated. The expression of BAFF receptor (BAFF-R) and downstream signal transduction were explored. The influence of BAFF on the expression of related genes was also studied.
Our data indicated that BAFF had a proliferative effect on human mesangial cells, as supported by the results of cell proliferation assays and the inhibited expression of the pro-apoptotic gene Bim. BAFF-R was expressed on the cell membrane of human mesangial cells and blockade of BAFF/BAFF-R binding abrogated the proliferative effect of BAFF on human mesangial cells. BAFF stimulation led to rapid phosphorylation of NF-κBp65, Akt and MAPK p38 kinase in human mesangial cells, whereas it had no effect on the expression of NF-κB p100 and phosphorylation of Erk. The phosphorylation of Akt was very sensitive to blockade of BAFF/BAFF-R ligation, although activation of MAPK p38 and NF-κBp65 was not. BAFF treatment resulted in decreased expression of BAFF-R, which implied negative feedback regulation after its binding.
BAFF promoted proliferation of human mesangial cells, which was mediated via BAFF-R. The BAFF/BAFF-R interaction triggered Akt, p65 and p38 activation, with Akt phosphorylation being tightly dependent on BAFF/BAFF-R interaction.
肿瘤坏死因子家族的B细胞激活因子（BAFF）对B细胞的存活、增殖和激活至关重要。有证据表明，在肾小球肾炎（如狼疮性肾炎、IgA肾病）中，BAFF在全身或局部水平升高。然而，BAFF对人系膜细胞的作用尚不清楚。
研究了BAFF对体外培养的人系膜细胞系增殖的影响。探讨了BAFF受体（BAFF-R）的表达及下游信号转导。还研究了BAFF对相关基因表达的影响。
我们的数据表明，细胞增殖试验结果及促凋亡基因Bim表达受抑制均支持BAFF对人系膜细胞有增殖作用。BAFF-R表达于人系膜细胞膜上，阻断BAFF/BAFF-R结合可消除BAFF对人系膜细胞的增殖作用。BAFF刺激导致人系膜细胞中NF-κB p65、Akt和丝裂原活化蛋白激酶p38激酶快速磷酸化，而对NF-κB p100的表达和Erk的磷酸化无影响。Akt的磷酸化对BAFF/BAFF-R连接的阻断非常敏感，而丝裂原活化蛋白激酶p38和NF-κB p65的激活则不然。BAFF处理导致BAFF-R表达降低，这意味着其结合后存在负反馈调节。
BAFF促进人系膜细胞增殖，这一过程由BAFF-R介导。BAFF/BAFF-R相互作用触发Akt、p65和p38激活，其中Akt磷酸化紧密依赖于BAFF/BAFF-R相互作用。
