CAPTOPRIL REVERSES HIGH-GLUCOSE-INDUCED GROWTH EFFECTS ON LLC-PK1 CELLS PARTLY BY DECREASING TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR PROTEIN EXPRESSIONS

Transforming growth factor beta (TGF-beta) may be important in the pat hogenesis of diabetic nephropathy, and captopril is effective in treat ing this disorder. However, the mechanisms of this therapeutic effect as related to TGF-beta and its receptors are not known. Thus, the effe cts of captopril on cellular growth, TGF-beta 1, and TGF-beta receptor s were studied in LLC-PK1 cells cultured in normal (11 mM) or high glu cose (27.5 mM). This study found that glucose dose-dependently inhibit ed cellular mitogenesis while inducing hypertrophy in these cells at 7 2 h of culture, concomitantly with enhanced TGF-beta 1 messenger RNA ( mRNA) and TGF-beta receptor Types I and II protein expressions, Captop ril dose-dependently (0.1 to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these cells. Moreover, captopril also decrea sed TGF-beta receptor Types I and II protein expressions dose-dependen tly. However, TGF-beta 1 mRNA was not affected by captopril. It was co ncluded that high glucose decreased cellular mitogenesis while increas ing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF-b eta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-ind uced growth effects by decreasing TGF-beta receptor protein expression s.