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学科主题临床医学
Synergistic Effect of Mesangial Cell-Induced CXCL1 and TGF-beta 1 in Promoting Podocyte Loss in IgA Nephropathy
Zhu, Li1,2,3,4; Zhang, Qingxian1,2,3,4; Shi, Sufang1,2,3,4; Liu, Lijun1,2,3,4; Lv, Jicheng1,2,3,4; Zhang, Hong1,2,3,4
刊名PLOS ONE
2013-08-30
DOI10.1371/journal.pone.0073425
8期:8
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]IMMUNE-COMPLEXES ; GRO-ALPHA ; IN-VITRO ; URINARY PODOCYTES ; KIDNEY-DISEASE ; POLYMERIC IGA ; INJURY ; EXPRESSION ; RECEPTORS ; TRANSPLANTATION
英文摘要

Podocyte loss has been reported to relate to disease severity and progression in IgA nephropathy (IgAN). However, the underlying mechanism for its role in IgAN remain unclear. Recent evidence has shown that IgA1 complexes from patients with IgAN could activate mesangial cells to induce soluble mediator excretion, and further injure podocytes through mesangial-podocytic cross-talk. In the present study, we explored the underlying mechanism of mesangial cell-induced podocyte loss in IgAN. We found that IgA1 complexes from IgAN patients significantly up-regulated the expression of CXCL1 and TGF-beta 1 in mesangial cells compared with healthy controls. Significantly higher urinary levels of CXCL1 and TGF-beta 1 were also observed in patients with IgAN compared to healthy controls. Moreover, IgAN patients with higher urinary CXCL1 and TGF-beta 1 presented with severe clinical and pathological manifestations, including higher 24-hour urine protein excretion, lower eGFR and higher cresentic glomeruli proportion. Further in vitro experiments showed that increased podocyte death and reduced podocyte adhesion were induced by mesangial cell conditional medium from IgAN (IgAN-HMCM), as well as rhCXCL1 together with rhTGF-beta 1. In addition, the over-expression of CXCR2, the receptor for CXCL1, by podocytes was induced by IgAN-HMCM and rhTGF-beta 1, but not by rhCXCL1. Furthermore, the effect of increased podocyte death and reduced podocyte adhesion induced by IgAN-HMCM and rhCXCL1 and rhTGF-beta 1 was rescued partially by a blocking antibody against CXCR2. Moreover, we observed the expression of CXCR2 in urine exfoliated podocytes in IgAN patients. Our present study implied that IgA1 complexes from IgAN patients could up-regulate the secretion of CXCL1 and TGF-beta 1 in mesangial cells. Additionally, the synergistic effect of CXCL1 and TGF-beta 1 further induced podocyte death and adhesion dysfunction in podocytes via CXCR2. This might be a potential mechanism for podocyte loss observed in IgAN.

语种英语
WOS记录号WOS:000323880200077
项目编号81000297 ; 2012CB517700 ; 81021004 ; 7131016
资助机构National Science Foundation for Youths of China ; Major State Basic Research Development Program of China (973 program) ; National Natural Science Foundation for Innovative Research Groups of China ; Beijing Natural Science Foundation
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53026
专题北京大学第一临床医学院_肾脏内科
北京大学第二临床医学院_肾内科
作者单位1.Peking Univ, Hosp 1, Dept Med, Div Renal, Beijing 100871, Peoples R China
2.Peking Univ, Inst Nephrol, Beijing 100871, Peoples R China
3.Minist Hlth China, Key Lab Renal Dis, Beijing, Peoples R China
4.Peking Univ, Minist Educ, Key Lab Chron Kidney Dis Prevent & Treatment, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Zhu, Li,Zhang, Qingxian,Shi, Sufang,et al. Synergistic Effect of Mesangial Cell-Induced CXCL1 and TGF-beta 1 in Promoting Podocyte Loss in IgA Nephropathy[J]. PLOS ONE,2013,8(8).
APA Zhu, Li,Zhang, Qingxian,Shi, Sufang,Liu, Lijun,Lv, Jicheng,&Zhang, Hong.(2013).Synergistic Effect of Mesangial Cell-Induced CXCL1 and TGF-beta 1 in Promoting Podocyte Loss in IgA Nephropathy.PLOS ONE,8(8).
MLA Zhu, Li,et al."Synergistic Effect of Mesangial Cell-Induced CXCL1 and TGF-beta 1 in Promoting Podocyte Loss in IgA Nephropathy".PLOS ONE 8.8(2013).
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