Connective tissue growth factor in human liver cirrhosis

被引:90
作者
Abou-Shady, M
Friess, H [1 ]
Zimmermann, A
di Mola, FF
Guo, XZ
Baer, HU
Büchler, MW
机构
[1] Univ Bern, Inselspital, Dept Visceral & Transplantat Surg, CH-3010 Bern, Switzerland
[2] Univ Bern, Dept Pathol, CH-3010 Bern, Switzerland
来源
LIVER | 2000年 / 20卷 / 04期
关键词
liver cirrhosis; CTGF; TGF-beta; fibrogenesis; Northern blot analysis; in situ hybridization;
D O I
10.1034/j.1600-0676.2000.020004296.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Connective tissue growth factor (CTGF) belongs to a family of factors that regulate fibrogenesis and wound healing. While the significance of transforming growth factor beta (TGF-beta) in liver fibrosis is well established, the role of CTGF in fibrosing hepatopathy is still unknown. Methods: CTGF was analyzed in 10 normal and in 16 cirrhotic liver tissue samples. Northern blot analysis was used to examine the concomitant expression of CTGF and TGF-PL mRNAs, and the cellular localization of CTGF mRNA was studied by in situ hybridization. For identification of myofibroblasts and activated hepatic stellate cells, alpha-smooth muscle actin (alpha-SMA) immunohistochemistry was used. Results: Northern blot analysis showed 6.5-fold enhanced expression of CTGF mRNA and 7.8-fold enhanced expression of TGF-beta 1 mRNA in liver cirrhosis in comparison with normal controls (p<0.01). By bt situ hybridization, CTGF mRNA was detectable in only a few spindle cells in the portal tracts in normal liver samples. In contrast, there was strong expression of CTGF mRNA in fibroblasts and myofibroblast-like cells present in fibrous septa surrounding the cirrhotic nodules, in stellate cells, in endothelial cells and in mesenchymal cells around ductular proliferations, and in ductular epithelial cells. There was a strong correlation between CTGF mRNA and TGF-beta 1 mRNA as well as the degree of fibrosis (p<0.01). Conclusions: Overexpression of CTGF in liver cirrhosis, especially in fibroblasts/myofibroblasts and stellate cells, suggests that this novel factor may play an important role in hepatic fibrosis.
引用
收藏
页码:296 / 304
页数:9
相关论文
共 36 条
  • [1] FORMATION OF EXTRACELLULAR-MATRIX IN NORMAL RAT-LIVER - LIPOCYTES AS A MAJOR SOURCE OF PROTEOGLYCAN
    ARENSON, DM
    FRIEDMAN, SL
    BISSELL, DM
    [J]. GASTROENTEROLOGY, 1988, 95 (02) : 441 - 447
  • [2] CELL-SPECIFIC EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA IN RAT-LIVER - EVIDENCE FOR AUTOCRINE REGULATION OF HEPATOCYTE PROLIFERATION
    BISSELL, DM
    WANG, SS
    JARNAGIN, WR
    ROLL, FJ
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (01) : 447 - 455
  • [3] 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
    BRADHAM, DM
    IGARASHI, A
    POTTER, RL
    GROTENDORST, GR
    [J]. JOURNAL OF CELL BIOLOGY, 1991, 114 (06) : 1285 - 1294
  • [4] MYOFIBROBLASTS IN FOCAL NODULAR HYPERPLASIA OF THE LIVER
    CALLEA, F
    MEBIS, J
    DESMET, VJ
    [J]. VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY, 1982, 396 (02) : 155 - 166
  • [5] INVITRO AND INVIVO ASSOCIATION OF TRANSFORMING GROWTH FACTOR-BETA-1 WITH HEPATIC-FIBROSIS
    CZAJA, MJ
    WEINER, FR
    FLANDERS, KC
    GIAMBRONE, MA
    WIND, R
    BIEMPICA, L
    ZERN, MA
    [J]. JOURNAL OF CELL BIOLOGY, 1989, 108 (06) : 2477 - 2482
  • [6] Overexpression of the epidermal growth factor receptor family in gastric cancer suggests a role in tumor pathogenesis
    Deflorin, J
    Friess, H
    Schobinger, S
    Brundler, MA
    Schilling, M
    Naef, M
    Korc, M
    Buchler, MW
    [J]. DIGESTIVE SURGERY, 1997, 14 (04) : 252 - 259
  • [7] FRANZIER K, 1996, J INVEST DERMATOL, V107, P404
  • [8] Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis
    Friess, H
    Cantero, D
    Graber, H
    Tang, WH
    Guo, XZ
    Kashiwagi, M
    Zimmermann, A
    Gold, L
    Korc, M
    Buchler, MW
    [J]. GASTROENTEROLOGY, 1997, 113 (03) : 904 - 913
  • [9] Enhanced expression of TGF-βs and their receptors in human acute pancreatitis
    Friess, H
    Lu, Z
    Riesle, E
    Uhl, W
    Bründler, AM
    Horvath, L
    Gold, LI
    Korc, M
    Büchler, MW
    [J]. ANNALS OF SURGERY, 1998, 227 (01) : 95 - 104
  • [10] Grotendorst GR, 1996, CELL GROWTH DIFFER, V7, P469