scholarly journals Morroniside Promotes PGC-1α-Mediated Cholesterol Efflux in Sodium Palmitate or High Glucose-Induced Mouse Renal Tubular Epithelial Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Junwei Gao ◽  
Peng Liu ◽  
Zhengri Shen ◽  
Ke Xu ◽  
Chenguang Wu ◽  
...  
Keyword(s):  
High Glucose ◽  
Cholesterol Efflux ◽  
Sodium Palmitate ◽  
Lipid Deposition ◽  
Tubular Epithelial Cells ◽  
Cholesterol Accumulation ◽  
Intracellular Lipid ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Renal Tubular

Lipid deposition is an etiology of renal damage caused by lipid metabolism disorder in diabetic nephropathy (DN). Thus, reducing lipid deposition is a feasible strategy for the treatment of DN. Morroniside (MOR), an iridoid glycoside isolated from the Chinese herb Cornus officinalis Sieb. et Zucc., is considered to be an effective drug in inhibiting oxidative stress, reducing inflammatory response, and countering apoptosis. To explore the protective mechanism of MOR in attenuating renal lipotoxicity in DN, we investigated the effect of MOR on an in vitro model of lipid metabolism disorder of DN established by stimulating mouse renal tubular epithelial cells (mRTECs) with sodium palmitate (PA) or high glucose (HG). Oil Red O and filipin cholesterol staining assays were used to determine intracellular lipid accumulation status. Results revealed that PA or HG stimulation inhibited the expressions of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), liver X receptors (LXR), ATP-binding cassette subfamily A member 1 (ABCA1), ABCG1, and apolipoprotein E (ApoE) in mRTECs as evidenced by western blot and quantitative real-time PCR, resulting in increased intracellular lipid deposition. Interestingly, MOR upregulated expressions of PGC-1α, LXR, ABCA1, ABCG1, and ApoE, thus reducing cholesterol accumulation in mRTECs, suggesting that MOR might promote cholesterol efflux from mRTECs via the PGC-1α/LXR pathway. Of note, silencing PGC-1α reversed the promotive effect of MOR on PA- or HG-induced cellular cholesterol accumulation. In conclusion, our results suggest that MOR has a protective effect on mRTECs under high lipid or high glucose conditions, which may be related to the promotion of intracellular cholesterol efflux mediated by PGC-1α.

High glucose aggravates lipid deposition in glomerular endothelial cells by LXRs/LncRNAOR13C9/ABCA1 pathway

2020 ◽  
Author(s):  
Shumin Xiao ◽  
Yao Wang ◽  
Saijun Zhou ◽  
Rui Zhang ◽  
Hongyan Liu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Cellular Response ◽  
Cell Activity ◽  
Lipid Deposition ◽  
High Cholesterol ◽  
Intracellular Lipid ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Glomerular Endothelial Cells

Abstract Background Lipid metabolism disorder is closely related to diabetic nephropathy (DN), but the mechanism remains unclear. The aim of this study was to investigate the effect of high glucose on intracellular accumulation of lipids and to clarify the possible mechanism. Methods We found that in human glomerular endothelial cells (GEnCs), cholesterol could reduce cell activity, lead to abnormal lipid deposition in cells and high glucose can aggravate lipid deposition under high cholesterol load. Results CCK8 showed that soluble cholesterol could reduce GEnCs cells activity. Oil red O staining and cholesterol quantification experiment showed that the intracellular lipid deposition did not obvious after the intervention of high glucose (HG), but the intracellular lipid deposition increased under HG combined with high cholesterol (HC). The results of RT-qPCR,WB and immunofluorescence experiment showed the expression of ABCA1 in HC group increased significantly. However, compared with the HC group, the expression of ABCA1in the HG and HC group were decreased. And then we found HG affected ABCA1 up-regulation by LXRs. Based on Gene Microarray, we found that LXRs regulation of ABCA1 transcription requires the involvement of LncRNAOR13C9. Conclusions HG could enhance intracellular lipid deposition by interfering with cellular response to HC to up-regulate the expression of ABCA1, and HG blocked the expression of ABCA1 by down-regulating LXRs, and LncRNAOR13C9 also played an important role in this process. It further elucidate the pathogenesis of DN and provide a new target for the prevention and treatment of DN.

scholarly journals CD36 promotes NLRP3 inflammasome activation via the mtROS pathway in renal tubular epithelial cells of diabetic kidneys

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yanjuan Hou ◽  
Qian Wang ◽  
Baosheng Han ◽  
Yiliang Chen ◽  
Xi Qiao ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Inflammasome Activation ◽  
Ros Production ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Nlrp3 Inflammasome Activation ◽  
Ampk Activity ◽  
Renal Tubular ◽  
Tubulointerstitial Inflammation

AbstractTubulointerstitial inflammation plays a key role in the pathogenesis of diabetic nephropathy (DN). Interleukin-1β (IL-1β) is the key proinflammatory cytokine associated with tubulointerstitial inflammation. The NLRP3 inflammasome regulates IL-1β activation and secretion. Reactive oxygen species (ROS) represents the main mediator of NLRP3 inflammasome activation. We previously reported that CD36, a class B scavenger receptor, mediates ROS production in DN. Here, we determined whether CD36 is involved in NLRP3 inflammasome activation and explored the underlying mechanisms. We observed that high glucose induced-NLRP3 inflammasome activation mediate IL-1β secretion, caspase-1 activation, and apoptosis in HK-2 cells. In addition, the levels of CD36, NLRP3, and IL-1β expression (protein and mRNA) were all significantly increased under high glucose conditions. CD36 knockdown resulted in decreased NLRP3 activation and IL-1β secretion. CD36 knockdown or the addition of MitoTempo significantly inhibited ROS production in HK-2 cells. CD36 overexpression enhanced NLRP3 activation, which was reduced by MitoTempo. High glucose levels induced a change in the metabolism of HK-2 cells from fatty acid oxidation (FAO) to glycolysis, which promoted mitochondrial ROS (mtROS) production after 72 h. CD36 knockdown increased the level of AMP-activated protein kinase (AMPK) activity and mitochondrial FAO, which was accompanied by the inhibition of NLRP3 and IL-1β. The in vivo experimental results indicate that an inhibition of CD36 could protect diabetic db/db mice from tubulointerstitial inflammation and tubular epithelial cell apoptosis. CD36 mediates mtROS production and NLRP3 inflammasome activation in db/db mice. CD36 inhibition upregulated the level of FAO-related enzymes and AMPK activity in db/db mice. These results suggest that NLRP3 inflammasome activation is mediated by CD36 in renal tubular epithelial cells in DN, which suppresses mitochondrial FAO and stimulates mtROS production.

scholarly journals Nox4 is involved in high glucose-induced apoptosis in renal tubular epithelial cells via Notch pathway

2017 ◽  
Vol 15 (6) ◽  
pp. 4319-4325 ◽  
Author(s):  
Min Yao ◽  
Feng Gao ◽  
Xiaomeng Wang ◽  
Yonghong Shi ◽  
Shuxia Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
High Glucose ◽  
Notch Pathway ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular ◽  
Induced Apoptosis
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