title: BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R.
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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. zhnuoy@mail.sysu.edu.cn.|Translational Medical Center, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. zhnuoy@mail.sysu.edu.cn.
authors.forename: Nuoyan
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. 2592272098@qq.com.|Translational Medical Center, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. 2592272098@qq.com.
authors.forename: Donxian
authors.initials: D
authors.lastname: Wang
authors.affiliation: International Travel Health Care Center, Entry & Exit Inspection and Quarantine Bureau of Guangdong Province, Guangdong, China. mhy_lucky@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ming
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. qingzh123@163.com.|Translational Medical Center, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. qingzh123@163.com.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Sun Sat-yet University, Guangzhou, China. yuxq@mail.sysu.edu.cn.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000494:pharmacology*; D053265:B-Cell Activation Factor Receptor / Q000187:drug effects* / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D051996:Transcription Factor RelA; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases