Hou Y.,Hebei Key Laboratory of Kidney Diseases |
Hou Y.,Hebei Medical University |
Wu M.,Hebei Medical University |
Wei J.,Hebei Key Laboratory of Kidney Diseases |
And 11 more authors.
Biochemical and Biophysical Research Communications | Year: 2015
The epithelial-to-mesenchymal transition (EMT) plays an important role in the progression of diabetic nephropathy. Our recent study showed that ROS mediated high glucose (HG)-induced EMT in renal tubular epithelial cells. CD36, a class-B scavenger receptor, has been reported to mediate the production of ROS in chronic kidney disease. In the present study, we examined the effect of inhibition of CD36 with CD36 siRNA or sulfosuccinimidyl-oleate (SSO), a CD36 antagonist, on HG-induced EMT in HK-2 cells. HG induced CD36 expression in a time-dependent manner in HK-2 cells. HG was shown to induce EMT at 72 h. This was blocked by knockdown of CD36 or treatment with SSO. Meanwhile, we also found that knockdown of CD36 or treatment with SSO inhibited HG-induced ROS generation, activation of ERK1/2 and Smad2, expression of TGF-β1 and synthesis of fibronectin. These data suggest that inhibition of CD36 prevented HG-induced EMT in HK-2 cells, highlighting CD36 as a potential therapeutic target for diabetic nephropathy. © 2015 Elsevier Inc. All rights reserved. Source
Du C.,Hebei Medical University |
Du C.,Hebei Key Laboratory of Kidney Diseases |
Shi Y.,Hebei Medical University |
Shi Y.,Hebei Key Laboratory of Kidney Diseases |
And 14 more authors.
Drug Design, Development and Therapy | Year: 2015
The dysregulation of cholesterol metabolism and inflammation plays a significant role in the progression of diabetic nephropathy (DN). Anthocyanins are polyphenols widely distributed in food and exert various biological effects including antioxidative, anti-inflammatory, and antihyperlipidemic effects. However, it remains unclear whether anthocyanins are associated with DN, and the mechanisms involved in the reciprocal regulation of inflammation and cholesterol efflux are yet to be elucidated. In this study, we evaluated the regulation of cholesterol metabolism and the anti-inflammatory effects exerted by anthocyanins (cyanidin-3-O-β-glucoside chloride [C3G] or cyanidin chloride [Cy]) and investigated the underlying molecular mechanism of action using high-glucose (HG)-stimulated HK-2 cells. We found that anthocyanins enhanced cholesterol efflux and ABCA1 expression markedly in HK-2 cells. In addition, they increased peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptor alpha (LXRα) expression and decreased the HG-induced expression of the proinflammatory cytokines intercellular adhesion molecule-1 (ICAM1), monocyte chemoattractant protein-1 (MCP1), and transforming growth factor-β1 (TGFβ1), as well as NFκB activation. Incubation with the PPARα-specific inhibitor GW6471 and LXRα shRNA attenuated the anthocyanin-mediated promotion of ABCA1 expression and cholesterol efflux, suggesting that anthocyanins activated PPARα-LXRα-ABCA1-dependent cholesterol efflux in HK-2 cells. Moreover, the knockout of LXRα abrogated the anti-inflammatory effect of anthocyanins, whereas the PPARα antagonist GW6471 does not have this effect. Further investigations revealed that LXRα might interfere with anthocyanin-induced decreased ICAM1, MCP1, and TGFβ1 expression by reducing the nuclear translocation of NFκB. Collectively, these findings suggest that blocking cholesterol deposition and inhibiting the LXRα pathway-induced inflammatory response might be one of the main mechanisms by which anthocyanins exert their protective effects in DN. © 2015 Du et al. Source