Abstract
Purpose: To investigate the anti-fibrotic effects of tanshinone IIA (TS) on renal tubular epithelial cells (HK-2 cells) under high glucose conditions and their related molecular mechanism(s) of action.Methods: After treatment with TS (6 μg/mL) for 24 h, the morphology of HK-2 cells stimulated by high glucose was observed under the microscope. Additionally, potential mechanisms related to the antifibrosis effects of TS were evaluated using western blotting assay and quantitative real time PCR (qRTPCR), including transforming growth factor (TGF) β1, α-smooth muscle actin (α-SMA), heme oxygenase 1 (HO-1), laminin (LN), fibronectin (FN), and E-cadherin (E-cad).Results: A high-glucose culture environment induced fibrosis of HK-2 cells, as indicated by changes in cell morphology. The anti-fibrotic effects of TS were mainly associated with a decrease in the expression levels of TGF-β1, α-SMA and LN, while the expression of E-cad increased. These resultsalso revealed that TS increased the expressions of HO-1.Conclusion: The findings suggest that TS suppresses fibrosis caused by high glucose in HK-2 cells by inhibiting extracellular matrix deposition and epithelial-mesenchymal transition and by reducing oxidative stress. Further investigations are needed to evaluate the clinical application of this compound in diabetic nephropathy.
 Keywords: Tanshinone IIA, Diabetic nephropathy, HK-2 cells, Fibrosis
Highlights
Diabetic nephropathy (DN) is a chronic microvascular complication of diabetes mellitus (DM)
Fibrosis is induced by high glucose environment in HK-2 cells
In HK-2 cells stimulated with high glucose levels, we observed that renal tubular epithelial cells lost their intrinsic morphology, resembling a long spindle-like fibroblast, and that the nucleus showed a spindle-like shape (Figure 1 B)
Summary
Diabetic nephropathy (DN) is a chronic microvascular complication of diabetes mellitus (DM). Accumulating scientific reports have revealed lots of extracts or compounds from natural herbal medicines that have medicinal properties for the prevention or treatment of diabetes mellitus and its complications [4,5]. Tanshinone IIA (TS), a medicinal component of Radix Salviae Miltiorrhizae, has a protective effect on the heart [6], is mainly used for the treatment of cardiovascular and cerebrovascular diseases. It has been reported that TS show protective effects on diabetic nephropathy [5]; the molecular mechanisms involved are still unclear. In this study, we aimed to explore the anti-fibrotic effects of TS on HK-2 cells (under high glucose conditions) and the molecular mechanisms involved, providing evidence for further research regarding TS in DN treatments
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