Decreased expression of smooth muscle alpha actin in activated rat hepaticstellate cells at the S-phase of the cell cycle in vitro

Hepatic stellate cells contain actin and myosin. and can contract in nature . With hepatocyte injury, these cells are activated to proliferate, change to a myofibroblast-like phenotype and produce extracellular matrices includ ing collagens. This activation is accompanied by increased expression of ce llular smooth muscle x actin. Generally, cells fail to exert specific funct ions during proliferation. The function of activated hepatic stellate cells was investigated in relation to the cell cycle. Hepatic stellate cells wer e isolated from normal rats and activated by culture on plastic dishes for 7 days. Western and Northern blot analyses revealed that these cells marked ly expressed smooth muscle x actin and transforming growth factor-beta (TGF -P) mRNA, When recombinant human platelet derived growth factor (PDGF)-BB w as added to the culture medium, such smooth muscle x actin expression was d ecreased in a dose-related manner, but TGF-P mRNA expression increased, DNA synthesis by these tells uas also increased, but collagen synthesis was un changed. Immunocytochemically, apparent staining of smooth muscle x actin H as seen in 9% of 5-bromo-2'-deoxyuridinr (BrdU)-positive cells. but in 80% of BrdU-negative cells. We conclude that hepatic stellate cells at the S-ph ase of the cell cycle after activation by culture express no, or less, smoo th muscle x actin. (C) 1999 Elsevier Science Ireland Ltd. All rights reserv ed.