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Interaction between high glucose and TGF-beta in cell cycle protein regulations in MDCK cells
1Department of Biochemistry, Kaohsiung Medical College, Taiwan, Republic of China.
Abstract:
Transforming growth factor-beta (TGF-beta) may mediate high glucose effects in renal cells. Thus, Madin-Darby canine kidney cells were studied for the modulation of cell cycle regulatory proteins by high glucose (27.5 mM) and TGF-beta1. We showed that unlike other renal cells, TGF-beta1 mRNA and its bioactivity were not induced by high-glucose culture. Furthermore, high glucose per se increased cellular proliferation without alterations in cell size. High glucose also increased the percentage of cells in the G2/M phase while decreasing cells in the G0/G1 phase of the cell cycle. In contrast, TGF-beta1 dose dependently (1 to 4 ng/ml) decreased cellular mitogenesis while increasing hypertrophy in the cells, especially in the presence of high glucose. TGF-beta1 also increased the percentage of cells arrested in the G0/G1 phase while decreasing cells in the G2/M phase of the cell cycle. Regarding two of the cell cycle regulatory proteins, high glucose increased cdc2 kinase activity and retinoblastoma protein (pRb) phosphorylation. In contrast, TGF-beta1 decreased cdc2 kinase activity and pRb phosphorylation, especially in the presence of high glucose. Additionally, glucose dose dependently (5.5, 16.5, 27.5, and 38.5 mM) increased type I and II TGF-beta receptor protein expression. In conclusion, changes in cdc2 kinase activity and pRb phosphorylation were correlated with high glucose and TGF-beta1-induced growth effects in a cell cycle-dependent manner in the Madin-Darby canine kidney cells. Furthermore, high glucose may potentiate TGF-beta1-induced effects by enhancing TGF-beta receptor protein expression.
Insights
High glucose and transforming growth factor-beta (TGF-beta) affect kidney cell growth differently. High glucose promotes cell proliferation, while TGF-beta inhibits it, but high glucose may enhance TGF-beta effects by increasing receptor expression.
Area of Science:
- Cell Biology
- Renal Physiology
- Molecular Endocrinology
Background:
- Transforming growth factor-beta (TGF-beta) is implicated in mediating high glucose effects in renal cells.
- Understanding the interplay between high glucose and TGF-beta1 in kidney cells is crucial for renal pathophysiology.
Purpose of the Study:
- To investigate the modulation of cell cycle regulatory proteins by high glucose and TGF-beta1 in Madin-Darby canine kidney cells.
- To elucidate the distinct and combined effects of high glucose and TGF-beta1 on cellular proliferation, cell cycle progression, and protein expression.
Main Methods:
- Madin-Darby canine kidney cells were cultured under high glucose (27.5 mM) and varying concentrations of TGF-beta1 (1-4 ng/ml).
- Cellular proliferation, cell size, cell cycle phase distribution (G0/G1, G2/M), cdc2 kinase activity, retinoblastoma protein (pRb) phosphorylation, and TGF-beta receptor expression were assessed.
Main Results:
- High glucose increased cellular proliferation and G2/M phase percentage, while TGF-beta1 decreased proliferation and increased G0/G1 arrest and hypertrophy.
- High glucose elevated cdc2 kinase activity and pRb phosphorylation, whereas TGF-beta1 decreased these parameters, particularly in the presence of high glucose.
- High glucose dose-dependently increased type I and II TGF-beta receptor protein expression.
Conclusions:
- Cell cycle regulatory protein changes correlate with high glucose and TGF-beta1-induced growth effects in a cell cycle-dependent manner.
- High glucose may potentiate TGF-beta1-induced effects in kidney cells by enhancing TGF-beta receptor expression.