Rhein inhibits renal tubular epithelial cell hypertrophy and extracellular matrix accumulation induced by transforming growth factor beta1
Abstract
Aim: To investigate the effects of rhein on cell hypertrophy and accumulation of extracellular matrix (ECM) in the renal tubular epithelial cells.
Methods: LLC-PK1 cells were incubated with transforming growth factor beta1 (TGFbeta1) 2 microg/L for 24 h to induce cell hypertrophy and production of ECM. To evaluate the effects of rhein on inhibiting the action of TGFbeta1, cell volume, cellular protein level, and [3H]leucine incorporation in LLC-PK1 cells treated with rhein at different concentrations were measured. In addition, the [3H]proline incorporation, level of fibronectin (FN) in supernatant, and mRNA expression of collagen IV and FN were also detected in rhein treated cells.
Results: The cell volume, cellular protein content, and [3H]leucine incorporation were markedly increased in LLC-PK1 cells after TGFbeta1 stimulation as compared with control (P < 0.01), and this TGFbeta1-stimulated cell hypertrophy was ameliorated by rhein. It was observed that TGFbeta1 not only increased the production of FN and [3H]proline incorporation in LLC-PK1 cells (P < 0.01), but also enhanced the mRNA expression of collagen IV and FN. Rhein significantly decreased the protein production and mRNA expression of ECM in LLC-PK1 cells stimulated by TGFbeta1.
Conclusion: Rhein can inhibit cell hypertrophy and ECM accumulation in LLC-PK1 cells induced by TGFbeta1, which may partly account for the role of rhein in preventing and retarding the progression of diabetic nephropathy.
Keywords:
Methods: LLC-PK1 cells were incubated with transforming growth factor beta1 (TGFbeta1) 2 microg/L for 24 h to induce cell hypertrophy and production of ECM. To evaluate the effects of rhein on inhibiting the action of TGFbeta1, cell volume, cellular protein level, and [3H]leucine incorporation in LLC-PK1 cells treated with rhein at different concentrations were measured. In addition, the [3H]proline incorporation, level of fibronectin (FN) in supernatant, and mRNA expression of collagen IV and FN were also detected in rhein treated cells.
Results: The cell volume, cellular protein content, and [3H]leucine incorporation were markedly increased in LLC-PK1 cells after TGFbeta1 stimulation as compared with control (P < 0.01), and this TGFbeta1-stimulated cell hypertrophy was ameliorated by rhein. It was observed that TGFbeta1 not only increased the production of FN and [3H]proline incorporation in LLC-PK1 cells (P < 0.01), but also enhanced the mRNA expression of collagen IV and FN. Rhein significantly decreased the protein production and mRNA expression of ECM in LLC-PK1 cells stimulated by TGFbeta1.
Conclusion: Rhein can inhibit cell hypertrophy and ECM accumulation in LLC-PK1 cells induced by TGFbeta1, which may partly account for the role of rhein in preventing and retarding the progression of diabetic nephropathy.