Upregulation of pleiotrophin expression in rat hepatic stellate cells by PDGF and hypoxia: Implications for its role in experimental biliary liver fibrogenesis

被引:31
作者
Antoine, M [1 ]
Tag, CG [1 ]
Wirz, W [1 ]
Borkham-Kamphorst, E [1 ]
Sawitza, I [1 ]
Gressner, AM [1 ]
Kiefer, P [1 ]
机构
[1] Rhein Westfal TH Aachen, Inst Clin Chem & Pathobiochem, D-5100 Aachen, Germany
关键词
pleiotrophin; anaplastic lymphoma kinase; heparin affin regulatory peptide; hepatic stellate cell; platelet derived growth factor; alpha-smooth muscle actin;
D O I
10.1016/j.bbrc.2005.09.173
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pleiotrophin (PTN) is a secretory heparin binding protein with various biological activities including mitogenesis, angiogenesis. and tissue repair after injury. Recent Studies have shown that PTN is a strong mitogen of hepatocytes and involved in liver regeneration. In adult liver cells Ptn gene is mainly expressed by quiescent hepatic stellate cells (HSCs). Although we have been able to demonstrate mRNA and protein expression of the anaplastic lymphoma kinase-the receptor tyrosine kinase for PTN-on HSCs, PTN did not act as a mitogen of HSCs in contrast to hepatocytes. PTN immunoreactivity was markedly increased in experimental fibrogenesis by common bile duct ligation and observed in sinusoidal HSCs. In primary HSC Cultures, Ptn transcription was significantly increased by PDGF-BB. and under hypoxic atmosphere. Mechanistically, hypoxia and PDGF mediated induction of PTN expression in sinusoidal HSCs may provide a strong mitogenic signal for hepatocytes to limit the damage to the parenchymal cells in biliary-type liver fibrogenesis. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:1153 / 1164
页数:12
相关论文
共 45 条
[1]   Hypoxic stimulation of vascular endothelial growth factor expression in activated rat hepatic stellate cells [J].
Ankoma-Sey, V ;
Wang, Y ;
Dai, ZH .
HEPATOLOGY, 2000, 31 (01) :141-148
[2]   Pleiotrophin/heparin-binding growth-associated molecule as a mitogen of rat hepatocytes and its role in regeneration and development of liver [J].
Asahina, K ;
Sato, H ;
Yamasaki, C ;
Kataoka, M ;
Shiokawa, M ;
Katayama, S ;
Tateno, C ;
Yoshizato, K .
AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (06) :2191-2205
[3]   Hepatic fibrosis as wound repair: A progress report [J].
Bissell, DM .
JOURNAL OF GASTROENTEROLOGY, 1998, 33 (02) :295-302
[4]   Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase [J].
Bowden, ET ;
Stoica, GE ;
Wellstein, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (39) :35862-35868
[5]  
BRAET F, 1994, LAB INVEST, V70, P944
[6]   Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers [J].
Cassiman, D ;
Libbrecht, L ;
Desmet, V ;
Denef, C ;
Roskams, T .
JOURNAL OF HEPATOLOGY, 2002, 36 (02) :200-209
[7]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[8]   Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis [J].
Corpechot, C ;
Barbu, V ;
Wendum, D ;
Kinnman, N ;
Rey, C ;
Poupon, R ;
Housset, C ;
Rosmorduc, O .
HEPATOLOGY, 2002, 35 (05) :1010-1021
[9]   Pleiotrophin: A cytokine with diverse functions and a novel signaling pathway [J].
Deuel, TF ;
Zhang, N ;
Yeh, HJ ;
Silos-Santiago, I ;
Wang, ZY .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2002, 397 (02) :162-171
[10]   Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [J].
Dooley, S ;
Hamzavi, J ;
Breitkopf, K ;
Wiercinska, E ;
Said, HM ;
Lorenzen, J ;
Ten Dijke, P ;
Gressner, AM .
GASTROENTEROLOGY, 2003, 125 (01) :178-191