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学科主题: 临床医学
题名:
Synergistic Effect of Mesangial Cell-Induced CXCL1 and TGF-beta 1 in Promoting Podocyte Loss in IgA Nephropathy
作者: 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
发表日期: 2013-08-30
DOI: 10.1371/journal.pone.0073425
卷: 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
所属项目编号: 81000297 ; 2012CB517700 ; 81021004 ; 7131016
项目资助者: 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
WOS记录号: WOS:000323880200077
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53026
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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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

Recommended Citation:
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).
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