Connective tissue growth factor is increased in plasma of type 1 diabetic patients with nephropathy

被引:92
作者
Roestenberg, P
van Nieuwenhoven, FA
Wieten, L
Boer, P
Diekman, T
Tiller, AM
Wiersinga, WM
Oliver, N
Usinger, W
Weitz, S
Schlingemann, RO
Goldschmeding, R
机构
[1] Univ Utrecht, Ctr Med, Dept Pathol, NL-3584 CX Utrecht, Netherlands
[2] Univ Utrecht, Ctr Med, Dept Hypertens & Nephrol, NL-3584 CX Utrecht, Netherlands
[3] Acad Med Ctr, Dept Endocrinol & Metab, Amsterdam, Netherlands
[4] Acad Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands
[5] FibroGen, San Francisco, CA USA
关键词
D O I
10.2337/diacare.27.5.1164
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - Connective tissue growth factor (CTGF) is strongly upregulated in Fibrotic disorders and has been hypothesized to play a role in the development and progression of diabetes complications. The aim of the present study was to investigate the possible association of plasma CTGF levels in type I diabetic patients with markers relevant to development of diabetes complications. RESEARCH DESIGN AND METHODS - Plasma CTGF levels (full-length and NH2-terminal fragments) were determined in 62 well-characterized patients with type 1 diabetes and in 21 healthy control subjects. Correlations of these plasma CTGF levels with markers of glycemic control, platelet activation, endothelial activation, nephropathy, and retinopathy were investigated. RESULTS - Elevated plasma NH2-terminal fragment of CTGF (CTGF-N) levels were detected in a subpopulation of type I diabetic patients and were associated with diabetic nephropathy. Stepwise regression analysis revealed contribution of atbuminuria, creatinine clearance, and duration of diabetes as predictors of plasma CTGF-N level. Elevation of plasma CTGF-N levels in patients with retinopathy was probably clue to renal comorbidity. CONCLUSIONS - Plasma CTGF-N levels are elevated in type 1 diabetic patients with nephropathy and appear to be correlated with proteinuria and creatinine clearance. Further studies will be needed to determine the relevance of plasma CTGF as a clinical marker and/or pathogenic factor in diabetic nephropathy.
引用
收藏
页码:1164 / 1170
页数:7
相关论文
共 31 条
[1]   Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-β [J].
Abreu, JG ;
Ketpura, NI ;
Reversade, B ;
De Robertis, EM .
NATURE CELL BIOLOGY, 2002, 4 (08) :599-604
[2]   Glomerular mRNAs in human type 1 diabetes: Biochemical evidence for microalbuminuria as a manifestation of diabetic nephropathy [J].
Adler, SG ;
Kang, SW ;
Feld, S ;
Cha, DR ;
Barba, L ;
Striker, L ;
Striker, G ;
Riser, BL ;
LaPage, T ;
Nast, CC .
KIDNEY INTERNATIONAL, 2001, 60 (06) :2330-2336
[3]  
American Diabetes Association, 2003, DIABETES CARE S1, V26, pS94
[4]   Characterization of 16- to 20-kilodalton (kDa) connective tissue growth factors (CTGFs) and demonstration of proteolytic activity for 38-kDa CTGF in pig uterine luminal flushings [J].
Ball, DK ;
Surveyor, GA ;
Diehl, JR ;
Steffen, CL ;
Uzumcu, M ;
Mirando, MA ;
Brigstock, DR .
BIOLOGY OF REPRODUCTION, 1998, 59 (04) :828-835
[5]   In vitro evidence for differential involvement of CTGF, TGFβ, and PDGF-BB in mesangial response to injury [J].
Blom, IE ;
van Dijk, AJ ;
Wieten, L ;
Duran, K ;
Ito, Y ;
Kleij, L ;
deNichilo, M ;
Rabelink, TJ ;
Weening, JJ ;
Aten, J ;
Goldschmeding, R .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2001, 16 (06) :1139-1148
[6]   Interactions of transforming growth factor-β and angiotensin II in renal fibrosis [J].
Border, WA ;
Noble, NA .
HYPERTENSION, 1998, 31 (01) :181-188
[7]   CONNECTIVE-TISSUE GROWTH-FACTOR - A CYSTEINE-RICH MITOGEN SECRETED BY HUMAN VASCULAR ENDOTHELIAL-CELLS IS RELATED TO THE SRC-INDUCED IMMEDIATE EARLY GENE-PRODUCT CEF-10 [J].
BRADHAM, DM ;
IGARASHI, A ;
POTTER, RL ;
GROTENDORST, GR .
JOURNAL OF CELL BIOLOGY, 1991, 114 (06) :1285-1294
[8]   The need for early predictors of diabetic nephropathy risk - Is albumin excretion rate sufficient? [J].
Caramori, ML ;
Fioretto, P ;
Mauer, M .
DIABETES, 2000, 49 (09) :1399-1408
[9]   Circulating and urinary transforming growth factor β1, Amadori albumin, and complications of type 1 diabetes -: The EURODIAB Prospective Complications Study [J].
Chaturvedi, N ;
Schalkwijk, CG ;
Abrahamian, H ;
Fuller, JH ;
Stehouwer, CDA .
DIABETES CARE, 2002, 25 (12) :2320-2327
[10]   Reversibility of established diabetic glomerulopathy by anti-TGF-β antibodies in dbldb mice [J].
Chen, S ;
Igleasias-de la Cruz, MC ;
Jim, B ;
Hong, SW ;
Isono, M ;
Ziyadeh, FN .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 300 (01) :16-22