Effect of serum IgA1 from patients with IgA nephropathy on the transforming growth factor -β1/Smads signaling pathway in human glomerular mesangial cells

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Author:
JIANG Xiao-yun(Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China)
WU Wei()
ZHANG Qiao-ling()
MO Ying(Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China)
CHEN Li-zhi(Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China)
LU Hui-yu(Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China)
CHEN Shu-mei(Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China)
Journal Title:
CHINESE JOURNAL OF BIOMEDICAL ENGINEERING
Issue:
Volume 15, Issue 04, 2009
DOI:
10.3760/cma.j.issn.1674-1927.2009.04.001
Key Word:
Glomerulonephritis;IgA;Mesangial cells;Transforming growth factor beta1;Phosphorylated Smad3;Fibronectins

Abstract: Objective To explore the effect of serum IgA1 from patients with IgA nephropathy(IgAN) on transforming growth factor beta- 1 ( TGF-β 1 ), phosphorylated Smad3 (p-Smad3) and fibronectin(FN) in human glomerular mesangial cells (HMC). Methods HMC was cultured in vitro and divided into 5 groups: IgA1 free control (health control group), stimulated with serum IgA1 from healthy people (NIgA1group) , stimulated with serum aggregated IgA1 from healthy people (aNIgA1 group) , stimulated with serum IgA1 from patients with IgA nephropathy (IgAN) (PIgA1 group), and stimulated with serum aggregated IgA 1 from patients with IgAN (aPIgA1 group). The expression of TGF-β1, p-Smad3 and FN mRNA was assayed by RT-PCR. The expression of p-Smad3 protein was analyzed by Western blot. The expression of TGF-β1 and FN protein in the culture supematant of HMC was analyzed by ELISA. Results PIgA1 and aPIgA1 significantly up-regnlated TGF-β1, p-Smad3, FN mRNA and protein expression. The TGF-β1, p-Smad3 and FN mRNA were increased by 1.5-fold(P<0.01), 1.3-fold(P<0.05) and 1.5-fold(P< 0.01 ) in aPIgA1 group as compared with PIgA1 group. The TGF-β1 and p-Smad3 protein were increased by 2.1-fold and 1.6-fold (P<0.01) in aPIgA1 group as compared with PIgA1 group. In aPIgA1 group, the expression of TGF-β1 and p-Smad3 mRNA with aPIgA1 was increased gradually, peaked at 12 h (0.866± 0.055,0.891±0.251 ), and then decreased to the basic levels at 24 h, but the the expression of FN mRNA peaked at 24 h(0.968±0.031 ). The expression of TGF-β1 and p-Smad3 protein was increased , peaked at 12 h for TGF-β1 [(246.960±1.270) ng/L], at 6 h for p-Smad3(0.490±0.046), then decreased. The expression of FN protein was increased , peaked at 24 h [(1.804±0.038) mg/L] (P<0.01). Conclusions PIgA1 and aPIgA1 significantly up-regulate TGF-β, p-Smad3, FN mRNA and protein expression. The effect of aPIgA1 is stronger than that of PIgA1. It is suggested that serum IgA1, mainly aIgA1 from patients with IgAN may play an important role in the progression of IgAN through TGF-β1/Smads signaling pathway.

  • [1]中华医学会儿科学分会肾脏病学组.33所医院儿童原发性IgAN临床和病理表现调查分析.中华儿科杂志,2007,45:272-278.
  • [2]Lai KN,Chan LY,Leung JC.Mechanisms of tubulointerstitial injury in IgA nephropathy.Kidney Int Suppl,2005,8:110-115.
  • [3]Yuan L,Wu YG,Hao L,et al.Effect of total glycosides of paeony on the expression of intercellular adhesion molecule-1 and transforming growth factor I protein in the kidney in experimental diabetes.Chin Pharmacol Bull,2007,23:821-826.
  • [4]Barratt J,Feehally J,Smith AC,et al.Pathogenesis of IgA nephropathy.Semin Nephrol,2004,24:197-217.
  • [5]Wyatt RJ,Kritchevsky SB,Woodford SY,et al.IgA nephropathy:long-term prognosis for pediatric patients.J Pediatr,1995,127:913-919.
  • [6]Li JH,Zhu HJ,Huang XR,et al.Smad7 inhibits fibrotic effect of TGF-beta on renal tubular epithelial cells by blocking Smad2 activation.J Am Soc Nephrol,2002,13:1464-1472.
  • [7]Wu W,Jiang XY,Zhang QL,et al.Expression and significance of TGF-β1/Smads signaling pathway in children with IgA nephropathy.WJP,2009,5:211-215.
  • [8]Ralf W,Masashi K,Jurgen F.IgA-nephropathy:how does IgA activate the mesangial cell ? Clin Exp Nephrol,2001,5:1-7.
  • [9]Leung JC,Tang AW,Chan DT,et al.Charge dependent binding of polymeric IgA1 to human mesangial cells in IgA nephropathy.Kidney Int,2001,59:277-285.
  • [10]王悦,赵明辉,章友康,等.IgA肾病患者血清IgA1诱导健康人肾小球系膜细胞钙离子释放、转化生长因子β表达上调和纤连蛋白分泌.中国病理生理杂志,2004,20:1025-1029.
  • [11]Lai KN,To WY,Li PK,et al.Increased binding of polymeric λ-IgA to cultured human mesangial cells in IgA nephropathy.Kidney Int,1996,49:839-845.
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