STIMULATORY EFFECT OF LIPOPROTEIN (A) ON PROLIFERATION OF HUMAN MESANGIAL CELLS - ROLE OF LIPOPROTEIN (A) IN RENAL-DISEASE

As lipoprotein (a) [Lp(a)] abnormalities would accelerate glomerular i njury, we studied the effect of Lp (a) on proliferation of cultured hu man mesangial cells (MC), Transfection of human apo (a) gene into huma n hepatoma cells, HepG2 cells, producing human apo B, resulted in the formation of Lp (a), while no Lp (a) was detected in control cells. In contrast, free apo (a) was detected in the medium of apo (a)-transfec ted RLC. Incubation of cultured medium of HepG2 cells transfected with apo (a) gene with MC resulted in a significant increase in cell numbe r compared to control (P < 0.01). In contrast, little effect of transf ection of apo (a) gene directly into MC on growth of MC was observed. Of importance, addition of LDL into the medium of MC transfected with apo (a) vector resulted in a significant increase in number of MC comp ared to control, whereas LDL did not show any effects on RLC growth. A s active TGF-beta was not detected in the medium of MC, and addition o f neutralizing anti-TGF-beta antibody did not alter growth of MC, Lp ( a) stimulated growth of MC via the independent mechanisms from the inh ibition of TGF-beta activation. (C) 1998 Academic Press.