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Captopril reverses high-glucose-induced growth effects on LLC-PK1 cells partly by decreasing transforming growth
1Department of Internal Medicine, Kaohsiung Medical College, Taiwan, Republic of China.
Abstract:
Transforming growth factor beta (TGF-beta) may be important in the pathogenesis of diabetic nephropathy, and captopril is effective in treating this disorder. However, the mechanisms of this therapeutic effect as related to TGF-beta and its receptors are not known. Thus, the effects of captopril on cellular growth, TGF-beta 1, and TGF-beta receptors were studied in LLC-PK1 cells cultured in normal (11 mM) or high glucose (27.5 mM). This study found that glucose dose-dependently inhibited cellular mitogenesis while inducing hypertrophy in these cells at 72 h of culture, concomitantly with enhanced TGF-beta 1 messenger RNA (mRNA) and TGF-beta receptor Types I and II protein expressions. Captopril dose-dependently (0.1 to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these cells. Moreover, captopril also decreased TGF-beta receptor Types I and II protein expressions dose-dependently. However, TGF-beta 1 mRNA was not affected by captopril. It was concluded that high glucose decreased cellular mitogenesis while increasing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF-beta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-induced growth effects by decreasing TGF-beta receptor protein expressions.
Insights
Captopril reverses high glucose effects in kidney cells by reducing TGF-beta receptor expression. This study clarifies how captopril impacts cellular growth and TGF-beta signaling in diabetic nephropathy models.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Diabetic nephropathy pathogenesis involves transforming growth factor beta (TGF-beta).
- Captopril is a known treatment, but its mechanism regarding TGF-beta and its receptors is unclear.
- Understanding these mechanisms is crucial for optimizing diabetic nephropathy treatment.
Purpose of the Study:
- To investigate the effects of captopril on cellular growth, TGF-beta 1, and TGF-beta receptors in LLC-PK1 cells under high glucose conditions.
- To elucidate the role of TGF-beta signaling in high-glucose-induced kidney cell changes.
- To determine if captopril modulates TGF-beta receptor expression.
Main Methods:
- LLC-PK1 cells were cultured in normal (11 mM) or high glucose (27.5 mM) media.
- Cells were treated with varying concentrations of captopril (0.1 to 10 mM).
- Cellular mitogenesis, hypertrophy, TGF-beta 1 mRNA, and TGF-beta receptor Types I and II protein expressions were analyzed.
Main Results:
- High glucose inhibited cell mitogenesis and induced hypertrophy, increasing TGF-beta 1 mRNA and receptor protein levels.
- Captopril dose-dependently enhanced cell mitogenesis and inhibited hypertrophy.
- Captopril decreased TGF-beta receptor Types I and II protein expression, but did not affect TGF-beta 1 mRNA.
Conclusions:
- High glucose negatively impacts kidney cell growth and increases TGF-beta signaling components.
- Captopril effectively counteracts high-glucose-induced cellular changes.
- Captopril's therapeutic effect may stem from its ability to downregulate TGF-beta receptor expression.