Lipid Nephrotoxicity: New Concept for an Old Disease

2014 ◽  
pp. 9-25
Author(s):  
Xiong Zhong Ruan ◽  
Zac Varghese ◽  
John Moorhead
Keyword(s):  
Lipid Nephrotoxicity

scholarly journals The question of primary lipid nephrotoxicity

2012 ◽  
Vol 27 (7) ◽  
pp. 2614-2615
Author(s):  
Margret Arnadottir
Keyword(s):  
Lipid Nephrotoxicity

scholarly journals FC 084LIPOTOXICITY MEDIATED BY GPR43 ACTIVATION CONTRIBUTES TO PODOCYTE INJURY IN DIABETIC NEPHROPATHY THROUGH MODULATING ERK/EGR1 PATHWAY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jian Lu ◽  
Jia Xiu Zhang ◽  
Pei Pei Chen ◽  
Xue Qi Li ◽  
Bicheng Liu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Knockout Mice ◽  
Cholesterol Metabolism ◽  
Synergistic Effects ◽  
Periodic Acid ◽  
Immunofluorescent Staining ◽  
Cholesterol Accumulation ◽  
Periodic Acid Schiff ◽  
Podocyte Injury ◽  
Lipid Nephrotoxicity

Abstract Background and Aims The G-protein-coupled receptor 43 (GPR43) is a post-transcriptional regulator involved in cholesterol metabolism. Our previous studies demonstrated that intracellular cholesterol accumulation contributed to podocyte injury in diabetic nephropathy (DN). This study aimed to investigate possible roles of GPR43 activation in lipid nephrotoxicity in DN and to explore its potential mechanisms. Method The experiments were conducted by using diabetic GPR43 knockout mice and cell culture model of podocytes. Renal pathological changes were checked by periodic acid schiff staining, immunohistochemical staining and transmission electron microscopy (TEM). The lipid deposition and free cholesterol contents in kidney tissues were detected by Oil Red O staining, BODIPY staining, and cholesterol quantitative assay. The protein expressions of GPR43, LC3II, p62 and related molecules of LDLR pathway in kidney tissues and podocytes were detected by real-time PCR, immunofluorescent staining, and Western blotting. Results There were decreased plasma level of LDL-cholesterol and cholesterol accumulation in kidney tissues of diabetic GPR43 knockout mice. In vitro study demonstrated that acetate, a stimulator of GPR43, increased LDLR-mediated cholesterol uptake in podocytes, accompanied with reduced cholesterol autophagic degeneration, characterized by inhibited LC3 maturation, p62 degradation, and autophagosome formation. These may evoke synergistic effects attributing to cellular cholesterol accumulation in podocytes. While genetic knockdown or pharmacological inhibition of GPR43 inhibited this effect in podocytes. Furthermore, the activation of GPR43 led to the activation of ERK1/2/EGR1 pathway in podocytes, whereas blocking ERK1/2 activity or reducing EGR1 expression reversed cholesterol influx and the inhibition of autophagy mediated by GPR43 activation in podocytes. Meanwhile, deletion of the GPR43 improved autophagy and inhibited the ERK1/2-EGR1 pathway of podocyte in diabetic mice in vivo. Conclusion Activation of the GPR43 mediated lipid nephrotoxicity contributes to podocyte injury in DN, which was mainly through the activation of ERK/EGR1 pathways. These findings suggested that the GPR43 receptor could be a potential therapeutic target for the prevention of DN progression.

Lipid Nephrotoxicity: New Concept for an Old Disease

2012 ◽  
Vol 14 (2) ◽  
pp. 177-181 ◽  
Author(s):  
Leonard Gyebi ◽  
Zohreh Soltani ◽  
Efrain Reisin
Keyword(s):  
Lipid Nephrotoxicity

scholarly journals THBS1/CD47 Modulates the Interaction of γ-Catenin With E-Cadherin and Participates in Epithelial–Mesenchymal Transformation in Lipid Nephrotoxicity

2021 ◽  
Vol 8 ◽  
Author(s):  
Li Gao ◽  
Ting-ting Yang ◽  
Jun-sheng Zhang ◽  
Hong-xia Liu ◽  
Dong-cheng Cai ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Real Time ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Histological Analysis ◽  
Tubular Epithelial Cells ◽  
High Fat ◽  
High Lipid ◽  
Lipid Nephrotoxicity ◽  
E Cadherin

Hyperlipidemia, an important risk factor for cardiovascular and end-stage renal diseases, often aggravates renal injury and compromises kidney function. Here, histological analysis of human kidney samples revealed that high lipid levels induced the development of renal fibrosis. To elucidate the mechanism underlying lipid nephrotoxicity, we used two types of mouse models (Apoe−/− and C57BL/6 mice fed a 45 and 60% high-fat diet, respectively). Histological analysis of kidney tissues revealed high-lipid-induced renal fibrosis and inflammation; this was confirmed by examining fibrotic and inflammatory marker expression using Western blotting and real-time polymerase chain reaction. Oxidized low-density lipoprotein (OX-LDL) significantly induced the fibrotic response in HK-2 tubular epithelial cells. RNA-sequencing and Gene Ontology analysis of differentially expressed mRNAs in OX-LDL-treated HK-2 tubular epithelial cells and real-time PCR validation in Apoe−/− mice showed that the expression of thrombospondin-1 (THBS1) in the high-fat group was significantly higher than that of the other top known genes, along with significant overexpression of its receptor CD47. THBS1 knockdown cells verified its relation to OX-LDL-induced fibrosis and inflammation. Liquid chromatography tandem mass spectrometry and STRING functional protein association network analyses predicted that THBS1/CD47 modulated the interaction between γ-catenin and E-cadherin and was involved in epithelial–mesenchymal transition, which was supported by immunoprecipitation and immunohistochemistry. CD47 downregulation following transfection with small-hairpin RNA in OX-LDL-treated tubular epithelial cells and treatment with anti-CD47 antibody restored the expression of E-cadherin and attenuated renal injury, fibrosis, and inflammatory response in OX-LDL-treated cells and in type 2 diabetes mellitus. These findings indicate that CD47 may serve as a potential therapeutic target in long-term lipid-induced kidney injury.

An update on the lipid nephrotoxicity hypothesis

2009 ◽  
Vol 5 (12) ◽  
pp. 713-721 ◽  
Author(s):  
Xiong Z. Ruan ◽  
Zac Varghese ◽  
John F. Moorhead
Keyword(s):  
Lipid Nephrotoxicity

Lipid Nephrotoxicity and Increased Risk of Nephrolithiasis in Model of Estrogen Deficiency

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Bryce J. Fiebiger ◽  
Jonathan I. Van Erdewyk ◽  
Khan Bilal ◽  
Victor Babich ◽  
Maria Barnes ◽  
...  
Keyword(s):  
Estrogen Deficiency ◽  
Increased Risk ◽  
Lipid Nephrotoxicity

scholarly journals The lipid nephrotoxicity hypothesis

2018 ◽  
Vol 48 (1) ◽  
pp. 47-55 ◽  
Author(s):  
XiongZhong RUAN
Keyword(s):  
Lipid Nephrotoxicity

LIPID NEPHROTOXICITY IN CHRONIC PROGRESSIVE GLOMERULAR AND TUBULO-INTERSTITIAL DISEASE

The Lancet ◽  
1982 ◽  
Vol 320 (8311) ◽  
pp. 1309-1311 ◽  
Author(s):  
J.F. Moorhead ◽  
M. El-Nahas ◽  
M.K. Chan ◽  
Z. Varghese
Keyword(s):  
Lipid Nephrotoxicity ◽  
Interstitial Disease
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