1. Academic Validation
  2. BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R

BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R

  • BMC Nephrol. 2015 May 15;16:72. doi: 10.1186/s12882-015-0064-y.
Nuoyan Zheng 1 2 Donxian Wang 3 4 Hongyan Ming 5 Haiqing Zhang 6 7 Xueqing Yu 8
Affiliations

Affiliations

  • 1 Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. zhnuoy@mail.sysu.edu.cn.
  • 2 Translational Medical Center, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. zhnuoy@mail.sysu.edu.cn.
  • 3 Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. 2592272098@qq.com.
  • 4 Translational Medical Center, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. 2592272098@qq.com.
  • 5 International Travel Health Care Center, Entry & Exit Inspection and Quarantine Bureau of Guangdong Province, Guangdong, China. mhy_lucky@163.com.
  • 6 Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. qingzh123@163.com.
  • 7 Translational Medical Center, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. qingzh123@163.com.
  • 8 Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. yuxq@mail.sysu.edu.cn.
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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