H. Tada et al., THROMBOSPONDIN MODULATES ADHESION, PROLIFERATION AND PRODUCTION OF EXTRACELLULAR-MATRIX IN MESANGIAL CELLS, Tohoku Journal of Experimental Medicine, 177(4), 1995, pp. 293-302
Thrombospondin (TSP) is produced by glomerular mesangial cells and one
of the extracellular matrix in the mesangium, whereas the physiologic
al role of TSP in mesangial cells is poorly understood. In order to kn
ow whether TSP modulates mesangial cell functions, we investigated the
effects of TSP on cell adhesion, proliferation, synthesis of extracel
lular matrix and serine proteinases in cultured human mesangial cells.
The substratum of TSP inhibited cell attachment and spreading in a TS
P-dose-dependent manner in mesangial cells. Soluble TSP (50 mu g/ml) a
lso caused the detachment of fully adherent mesangial cells, whereas T
SP less than 10 mu g/ml did not. [H-3]-thymidine incorporation into me
sangial cells was dose-dependently reduced by TSP. On the other hand,
the production of both fibronectin and type IV collagen from mesangial
cells was enhanced by TSP. The incubation of mesangial cells with TSP
increased the secretion of tissue-type plasminogen activator (tPA) an
d urokinase-type plasminogen activator (uPA), while plasminogen activa
tor inhibitor-type 1 (PAI-1) decreased. These observations indicate th
at TSP inhibits cell adhesion and proliferation in cultured human mesa
ngial cells. It is also suggested that TSP influences the metabolism o
f mesangial matrix by modulating both synthesis and degradation of mat
rix components. Thus, TSP may be an important mediator of mesangial ce
ll functions in an autocrine fashion.