Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-β1 Expression via Sphingosine Kinase 1 Pathway / 中国结合医学杂志

OBJECTIVE@#To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs).@*METHODS@#The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-β1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016.@*RESULTS@#LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1.@*CONCLUSION@#RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.

Effects of resveratrol on cell proliferation in glomerular mesangial cells cultured under high glucose by inhibiting SphK1/AP-1 signal pathway / 中国药理学通报

Aim To observe the expression of FN and TGF-β1 in the glomerular mesangial cells induced by high-glucose after the intervention of resveratrol, and further discuss its influence on SphK1/AP-1 signaling pathway. Methods The rat glomerular mesangial cells induced by high glucose were used to observe the effects of resveratrol on cell proliferation after interven-tion. The survival vitality and proliferation of glomeru-lar mesangial cells were determined by MTT, and then FN, TGF-β1 and SphK1 protein expression were deter-mined by Western blot. Also, AP-1 activity was deter- mined by EMSA assay. Results Resveratrol could obviously inhibit the proliferation of high glucose-in-duced glomerular mesangial cells, lower SphK1 expres-sion, inhibit AP-1 activity and thus inhibit the expres-sion of FN, TGF-β1. Conclusions Resveratrol inhib-its the proliferation of high glucose-induced glomerular mesangial cells, which may be closely related to the in-hibition of SphK1/AP-1 signaling pathway.

Change of serum associated factors in patients with combined pulmonary fibrosis and emphysema / 中国综合临床

Objective To investigate the levels of transformation growth factor-β1 (TGF-β1),vascular endothelial growth factor (VEGF) and insulin growth factor-Ⅰ (IGF-Ⅰ) role in the pathogenesis of serum of patients with combined pulmonary fibrosis and emphysema (CPFE).Methods Recruited 20 patients with CPFE,40 cases with idiopathic pulmonary interstitial fibrosis (IPF) and 40 cases with emphysema who were admitted to our hospital during July 2011 to February 2012.Serum levels of TGF-β1,VEGF and IGF-Ⅰ were detected by ABC-ELISA.Results Serum levels of TGF-β1 and IGF-Ⅰ were significantly higher in patients with CPFE and IPF than these in patients with emphysema (TGF-β1:(160.73 ± 40.62) ng/L vs.(167.35 ± 42.82) ng/L vs.(128.75 ±35.77) ng/L; IGF-Ⅰ:(179.65 ±60.73) ng/L vs.(192.32 ±58.75) ng/L vs.(148.73 ±49.67) ng/L,P ＜ 0.05 or P ＜ 0.01).The IPF group had significantly higher serum level of VEGF than the emphysema group ((506.12 ±82.37) ng/L vs.(437.31 ±62.58) ng/L,P ＜0.01).Serum levels of TGF-β1 and IGF-Ⅰ in CPFE and emphysema groups were positively correlated (r =0.885,0.918 respectively,P ＜ 0.01).Smokers in the CPFE group had significandy lower level of serum VEGF than those who did no smoke ((406.19 ± 66.94) ng/L vs.(482.88 ± 79.91) ng/L,t =-2.287,P =0.035).Conclusion Serum level of VEGF increased significantly in the IPF group,suggesting the participation of VEGF in pulmonary interstitial fibrosis.IGF-Ⅰ involved in the pathogenesis of pulmonary interstitial fibrosis.TGF-β1 and IGF-Ⅰ have a positive linear regressive relationship,which indicates that they may work synergistically in the process of the fibrosis.