Abstract
Triptolide as a main active ingredient of Tripterygium wilfordii is known to be exerting anti-inflammatory, marked immunosuppressive, and podocyte-protective effects. In this study, we investigated the protective effect of triptolide in kidney disease. Rat glomerular mesangial cells were randomly divided into three groups: (1) control group, (2) TGF-β1 (10 μg/mL) group, and (3) triptolide group (triptolide 10 μg/L + TGF-β1 10 μg/L). Sixty male Sprague-Dawley rats were randomly divided into three groups: (1) control group, (2) chronic serum sickness glomerulonephritis model group, and (3) triptolide (0.2 mg/kg·d) group. Reverse transcription PCR was used to assess Ski and Smad3 mRNA expression in the mesangial cells and renal tissues. Western blotting was used to determine Ski and Smad3 protein expressions. Laser confocal fluorescence microscopy was used to observe the subcellular localization of Smad3 and Ski proteins in the mesangial cells. Triptolide inhibited the TGF-β1-induced proliferation of mesangial cells. It significantly upregulated Ski protein expression and downregulated Smad3 mRNA and protein expressions in a time-dependent manner. Laser confocal fluorescence microscopy detected high Smad3 fluorescence intensity in the cytoplasm and low Smad3 and high Ski fluorescence intensity in the nucleus. By upregulating Ski protein expression triptolide decreased the extent of fibrosis by affecting the TGF-β1/Smad3 signaling pathway.
Highlights
Transforming growth factor-beta 1 (TGF-β1) is an important regulator of renal fibrosis and TGF-β1 gene activation, while its corresponding signaling protein Smad plays an important role in fibrosis in other organs and tissues [1]
TGF-β1 promotes the proliferation of mesangial cells, and the TGFβ1/Smad3 signal transduction pathway participates in renal fibrosis [2]
Cell proliferation was significantly lower after treatment with different concentrations of triptolide for different time points than that observed in the TGF-β1 group (P < 0.05)
Summary
Transforming growth factor-beta 1 (TGF-β1) is an important regulator of renal fibrosis and TGF-β1 gene activation, while its corresponding signaling protein Smad plays an important role in fibrosis in other organs and tissues [1]. TGF-β1 promotes the proliferation of mesangial cells, and the TGFβ1/Smad signal transduction pathway participates in renal fibrosis [2]. There is a very close relationship between the TGF-β1/Smad pathway and the Ski-SnoN protein family. TGF-β1 regulation is influenced by the expression of its receptor genes, the extent of its activation, and other factors such as the signal transduction pathway involving Smad when TGF-β1 combines with its corresponding receptors. Few studies have investigated the roles of Ski and the TGF-β1/Smad signaling pathway in renal fibrosis
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