Hyaluronic acid inhibits adhesion of hepatic stellate cells in spite of its stimulation of DNA synthesis

被引:12
作者
Cho, MK
Lee, GH
Park, EY
Kim, SG
机构
[1] Seoul Natl Univ, Coll Pharm, Natl Res Lab, Seoul 151742, South Korea
[2] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea
关键词
hepatic stellate cells; cell adhesion; hyaluronic acid; collagen; alpha-SMA; CD44;
D O I
10.1016/j.tice.2004.05.001
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Unbalanced accumulation of fibers in extracellular matrix (ECM) results from attachment and activation of hepatic stellate cells (HSCs) during chronic liver diseases, in which the content of hyaluronic acid (HA), a glycosaminoglycan, in ECM changes. No information is available on the effect of HA on adhesion and activation of HSCs although that of collagen (Col) on HSCs was extensively studied. This study investigated the effects of HA with or without Col on adhesion of HSCs or the rate of DNA synthesis. Attachment of primary cultured HSCs was microscopically monitored in the plate simultaneously coated with HA or other ECM components. HA inhibited adhesion of quiescent HSCs at least up to 7 days after seeding, whereas HSCs were adherent to plastic or type I collagen (Col-I), type III collagen (Col-III), type IV collagen (Col-IV) or fibronectin. Both microscopy and a-smooth muscle actin immunocytochemistry revealed that the number of HSCs, which had been re-seeded after 15 days of culture, attached to HA-coated area was remarkably lower compared to that of HSCs on Col-I or plastic. Incorporation of HA into Col-I prevented adhesion of activated HSCs to matrix film. The number of HSCs adherent to HA at early times after seeding was minimal and significantly lower than that of the cells adherent to plastic. In contrast, either Col-I or Col-IV increased the number of adherent cells. Attachment of HSCs to plastic was inhibited by soluble HA in culture medium. CD44, the cell surface receptor to which HA binds, was immunochemically detected in HSCs. Adhesion of HSCs to plastic, HA or Col-I was not changed by anti-CD44 antibody. Either HA or Col increased the basal or platelet-derived growth factor-inducible rate of thymidine incorporation into DNA in HSCs. In conclusion, HA inhibits adhesion of quiescent or activated HSCs in spite of its stimulation of DNA synthesis, whereas Col increases HSC attachment and DNA synthesis, and inhibition of HSC adhesion by HA does not involve CD44. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:293 / 305
页数:13
相关论文
共 36 条
[1]   Interaction of CD44 with different forms of hyaluronic acid. Its role in adhesion and migration of tumor cells [J].
Alaniz, L ;
Cabrera, PV ;
Blanco, G ;
Ernst, G ;
Rimoldi, G ;
Alvarez, E ;
Hajos, SE .
CELL COMMUNICATION AND ADHESION, 2002, 9 (03) :117-130
[2]  
Arthur MJP, 1998, J GASTROEN HEPATOL, V13, pS33
[3]   Hepatic stellate cells as a target for the treatment of liver fibrosis [J].
Bataller, R ;
Brenner, DA .
SEMINARS IN LIVER DISEASE, 2001, 21 (03) :437-451
[4]   Extracellular matrix degradation and the role of hepatic stellate cells [J].
Benyon, RC ;
Arthur, MJP .
SEMINARS IN LIVER DISEASE, 2001, 21 (03) :373-384
[5]   Cell-matrix interactions of in vitro human skin fibroblasts upon addition of hyaluronan [J].
Boraldi, F ;
Croce, MA ;
Quaglino, D ;
Sammarco, R ;
Carnevali, E ;
Tiozzo, R ;
Pasquali-Ronchetti, I .
TISSUE & CELL, 2003, 35 (01) :37-45
[6]   Hyaluronan - Is bigger better? [J].
Camenisch, TD ;
McDonald, JA .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 23 (04) :431-433
[7]   Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells [J].
Carloni, V ;
Romanelli, RG ;
Pinzani, M ;
Laffi, G ;
Gentilini, P .
GASTROENTEROLOGY, 1996, 110 (04) :1127-1136
[8]   Prevention of cultured rat stellate cell transformation and endothelin-B receptor upregulation by retinoic acid [J].
Chi, XD ;
Anselmi, K ;
Watkins, S ;
Gandhi, CR .
BRITISH JOURNAL OF PHARMACOLOGY, 2003, 139 (04) :765-774
[9]  
Du WD, 1999, WORLD J GASTROENTERO, V5, P397
[10]   Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells [J].
Failli, P ;
DeFranco, RMS ;
Caligiuri, A ;
Gentilini, A ;
Romanelli, RG ;
Marra, F ;
Batignani, G ;
Guerra, CT ;
Laffi, G ;
Gentilini, P ;
Pinzani, M .
GASTROENTEROLOGY, 2000, 119 (02) :479-492