Role of mast cells, stem cell factor and protease-activated receptor-2 in tubulointerstitial lesions in IgA nephropathy

被引:16
作者
Liu, Hong [1 ]
Liu, Fuyou [1 ]
Peng, Youming [1 ]
Liu, Yinghong [1 ]
Li, Lingyan [1 ]
Tu, Xiwen [1 ]
Cheng, Meichu [1 ]
Xu, Xiangqing [1 ]
Chen, Xing [1 ]
Ling, Guanghui [1 ]
Sun, Lin [1 ]
机构
[1] Cent S Univ, Xiangya Hosp 2, Inst Nephrol, Div Nephrol, Changsha 410011, Hunan, Peoples R China
关键词
IgA nephropathy; Mast cells; Stem cell factor; Protease-activated receptor-2; Tubulointerstitial fibrosis; SMOOTH-MUSCLE-CELLS; CULTURED FIBROBLASTS; MEMBRANOUS NEPHROPATHY; ENDOTHELIAL-CELLS; THROMBIN RECEPTOR; GROWTH-FACTOR; TRYPTASE; PROGRESSION; PAR-2; GLOMERULONEPHRITIS;
D O I
10.1007/s00011-010-0159-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To elucidate the role of mast cells (MCs) in the pathogenesis of tubulointerstitial lesions in IgA nephropathy (IgAN), we investigated the number of MCs, serum stem cell factor (SCF), protease-activated receptor-2 (PAR-2) and alpha-smooth-muscle actin (alpha-SMA) in the kidney and the correlation between MC number, SCF, PAR-2, alpha-SMA and tubulointerstitial lesions in biopsy specimens and serum creatinine levels, urinary protein excretion in patients with IgA nephropathy. Thirty-five patients with IgA nephropathy were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining. Monoclonal antibodies to human tryptase, alpha-SMA, and SCF and polyclonal antibody to PAR-2 were used as primary antibodies. Ten cortical interstitial fields were randomly selected and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields. In all of the control subjects, few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions, the expression of SCF, PAR-2 and alpha-SMA were positively correlated with the degree of interstitial fibrosis. A close correlation between MCs, alpha-SMA, PAR-2 and SCF was found (r = 0.887 for alpha-SMA, r = 0.844 for PAR-2, r = 0.853 for SCF, P < 0.01). Also a close correlation between alpha-SMA, PAR-2 and SCF was found (r = 0.874 for PAR-2, r = 0.862 for SCF, P < 0.01). PAR-2 was correlated with SCF (r = 0.893, P < 0.01). Moreover, a significant positive correlation was observed between the number of interstitial MCs, the expression of SCF, PAR-2 and alpha-SMA and the serum creatinine level (r = 0.738 for MCs, r = 0.658 for alpha-SMA, r = 0.692 for PAR-2, r = 0.754 for SCF, P < 0.05). Our findings suggest that MC infiltration possibly induced by SCF in renal interstitial tissues seems to be associated with tubulointerstitial fibrosis through PAR-2 in IgA nephropathy.
引用
收藏
页码:551 / 559
页数:9
相关论文
共 61 条
[1]   SIGNIFICANCE OF TUBULOINTERSTITIAL LESIONS IN BIOPSY SPECIMENS OF GLOMERULONEPHRITIC PATIENTS [J].
ABE, S ;
AMAGASAKI, Y ;
IYORI, S ;
KONISHI, K ;
KATO, E ;
SAKAGUCHI, H .
AMERICAN JOURNAL OF NEPHROLOGY, 1989, 9 (01) :30-37
[2]   Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2 [J].
Akers, IA ;
Parsons, M ;
Hill, MR ;
Hollenberg, MD ;
Sanjar, S ;
Laurent, GJ ;
McAnulty, RJ .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 278 (01) :L193-L201
[3]   IMMUNE-MECHANISMS IN IDIOPATHIC MEMBRANOUS NEPHROPATHY - THE ROLE OF THE INTERSTITIAL INFILTRATES [J].
ALEXOPOULOS, E ;
SERON, D ;
HARTLEY, RB ;
NOLASCO, F ;
CAMERON, JS .
AMERICAN JOURNAL OF KIDNEY DISEASES, 1989, 13 (05) :404-412
[4]  
ALPERS CE, 1994, J AM SOC NEPHROL, V5, P201
[5]  
Berger J., 1968, J UROL NEPHROL, V74, P694
[6]  
Bohle A, 1996, KIDNEY INT, V49, pS2
[7]   Induction of vascular smooth muscle cell growth by selective activation of the proteinase activated receptor-2 (PAR-2) [J].
Bono, F ;
Lamarche, I ;
Herbert, JM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 241 (03) :762-764
[8]  
BRADDING P, 1993, J IMMUNOL, V151, P3853
[9]   Liver granulomas in schistosomiasis: Mast cell-dependent induction of SCF expression in hepatic stellate cells is mediated by TNF-alpha [J].
Brito, JM ;
Borojevic, R .
JOURNAL OF LEUKOCYTE BIOLOGY, 1997, 62 (03) :389-396
[10]   TRYPTASE, THE DOMINANT SECRETORY GRANULAR PROTEIN IN HUMAN MAST-CELLS, IS A POTENT MITOGEN FOR CULTURED DOG TRACHEAL SMOOTH-MUSCLE CELLS [J].
BROWN, JK ;
TYLER, CL ;
JONES, CA ;
RUOSS, SJ ;
HARTMANN, T ;
CAUGHEY, GH .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1995, 13 (02) :227-236