<p>Resveratrol Inhibits Lipopolysaccharide-Induced Extracellular Matrix Accumulation and Inflammation in Rat Glomerular Mesangial Cells by SphK1/S1P2/NF-κB Pathway</p>

Abstract

Chronic inflammation plays a key role in the pathogenesis of various diseases such as diabetic nephropathy (DN). Resveratrol (RSV), a natural polyphenol, has been proven to have renoprotective effects. In this study, we used a lipopolysaccharide (LPS)induced rat glomerular mesangial cells (RMCs) model, to elucidate the renoprotective effect of RSV on sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1P2)/NF-κB activation and the expression of downstream inflammatory mediators, such as intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and fibronectin (FN) protein expression in RMCs. Methods: Cell proliferation was tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). The protein levels of FN, ICAM-1, iNOS, SphK1, S1P2 and NF-κB p65 in RMCs were detected by Western blot. The DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay (EMSA). SphK1 activity and S1P content were measured by using sphingosine kinase activity assay kit and ELISA assay, respectively. Results: We first found that LPS could stimulate SphK1/S1P axis activation, whereas this occurrence was significantly blocked by RSV pretreatment. RSV obviously repressed LPSinduced upregulated expression of fibronectin (FN), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) in RMCs. Moreover, RSV markedly reduced SphK1 activity and its protein expression, and attenuated S1P content in LPSinduced RMCs. Furthermore, RSV could block LPS-induced upregulation of NF-κB p65 and DNA-binding activity of NF-κB. And this phenomenon was notably attenuated by SphK1 inhibitor and S1P2 inhibitor. Conclusion: RSV inhibited LPS-induced RMCs' proliferation and inflammation and FN expression by SphK1/S1P2/NF-κB pathway, suggesting that RSV may be independent of its hypoglycemic effect on preventing or delaying the development of mesangial cell fibrosis.

Toll-like receptors 2 and 4 differentially regulate the self-renewal and differentiation of spinal cord neural precursor cells

“…All three tested downstream mediators of TLR2 and TLR4, induced nitric oxide synthase (iNOS), phosphorylated extracellular signal-regulated kinase (pERK), and interferon regulatory factor 1 (IRF1), displayed maximal activation (as measured by an increase in protein levels for iNOS and IRF1 and phosphorylation of ERK) 30 min after stimulation, with a decrease 30 min later (Fig. 2 E; representative Western blots shown on the left) as previously described in other cell types [ 41 , 42 ]. These data provided evidence for the responsive and functional nature of TLR2 and TLR4 to LPS by in vitro - expanded WT NPCs derived from mouse neonatal spinal cords.…”

Toll-Like Receptors 2 and 4 Differentially Regulate the Self-Renewal and Differentiation of Spinal Cord Neural Precursor Cells

“…All three tested downstream mediators of TLR2 and TLR4, induced nitric oxide synthase (iNOS), phosphorylated extracellular signal-regulated kinase (pERK), and interferon regulatory factor 1 (IRF1), displayed maximal activation (as measured by an increase in protein levels for iNOS and IRF1 and phosphorylation of ERK) 30 minutes after stimulation, with a decrease 30 minutes later (Fig. 2E; representative Western blots shown on the left) as previously described in other cell types [40,41]. These data provided evidence for the responsive and functional nature of TLR2 and TLR4 to LPS by in vitro-expanded WT NPCs derived from mouse neonatal spinal cords.…”

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

“…The early stage of DN is mainly characterized by abnormal renal hemodynamics, which mainly manifests as decreased vascular resistance in the glomerulus ( Toledo et al, 2015 ). Research has shown that accumulation of ECM production in the glomerular mesangial membrane may be related to NF-κB pathway ( Gong et al, 2020 ). The ameliorative effects of berberine (300 mg/kg) on ECM accumulation may be due to decreased TGF-β1 and ICAM-1 resulting from inhibition of the NF-κB pathway, as shown in a rat model of DN ( Liu et al, 2010a ).…”