INDUCTION OF CALPONIN-H1 BY TRANSFORMING GROWTH-FACTOR-BETA-1 IN CULTURED HUMAN ITO CELLS, LI90

We investigated the effect of transforming growth factor-beta 1 (TGF-b eta 1) on the expression of calponin-h1, alpha-smooth muscle actin (al pha-SMA), and extracellular matrix (ECM) components in a cultured huma n Ito cell line, LI90. The TGF-beta 1 treatment stimulated productions of hyaluronic acid and laminin, and significantly decreased the secre tion of hepatocyte growth factor in LI90 cells. The functional charact eristics of LI90 cells were compatible with those of human-activated I to cells that are known as pericyte-like mesenchymal liver cells. TGF- beta 1 induced a slight growth-inhibition of LI90 cells. TGF-beta 1 en hanced the expressions of both alpha-SMA and calponin-h1 at the protei n level, while tumor necrosis factor-alpha and interleukin-1 alpha did not affect the expressions of these cytoskeletal proteins on LI90 cel ls. The addition of TGF-beta 1 to LI90 cells resulted in a significant increase of calponin-h1 mRNA levels, but not calponin-h2. These data suggest that the expression of calponin-h1 is controlled at the level of mRNA under the coordinate regulation together with alpha-SMA as the process of perpetuation of activated Ito cells promoted by TGF-beta 1 . The identification of smooth muscle features promoted by TGF-beta 1 support the hypothesis that the activation of Ito cells coincides with their contractile behavior, indicating that these cells may be import ant in vasoregulation during liver injury and fibrosis. (C) 1998 Elsev ier Science B.V. All rights reserved.