CD36 Regulates Oxidative Stress and Inflammation in Hypercholesterolemic CKD

Okamura, Daryl M.; Pennathur, Subramaniam; Pasichnyk, Katie; López-Guisa, Jesús M.; Collins, Sarah; Febbraio, Maria; Heinecke, Jay W.; Eddy, Allison A.

doi:10.1681/asn.2008010009

Cited by 127 publications

(127 citation statements)

References 51 publications

(54 reference statements)

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…The HFD-induced and hypertriacylglycerolaemia-associated renal injury observed in this study may have been caused through activation of TLR4 by NEFA [25,26], oxidised LDL [27], or triacylglycerol-rich lipoproteins [6]. Previous studies have proposed that, by direct lipotoxicity on tubular epithelial cells, diet-induced obesity alone is sufficient to cause inflammatory and fibrotic changes in the whole kidney preparations through gene expression of Cd36 or sterol regulatory element-binding protein-1c (Srebp1c) [28][29][30]. In the present study, however, treatment of WT mice solely with HFD resulted in very mild renal lesions, probably because we used a diet with a lower fat content and studied the mice for a shorter period of time compared with earlier reports [28][29][30].…”

Section: Discussionmentioning

confidence: 68%

“…Previous studies have proposed that, by direct lipotoxicity on tubular epithelial cells, diet-induced obesity alone is sufficient to cause inflammatory and fibrotic changes in the whole kidney preparations through gene expression of Cd36 or sterol regulatory element-binding protein-1c (Srebp1c) [28][29][30]. In the present study, however, treatment of WT mice solely with HFD resulted in very mild renal lesions, probably because we used a diet with a lower fat content and studied the mice for a shorter period of time compared with earlier reports [28][29][30]. Furthermore, HFD increased glomerular Cd36 mRNA expression but STZ-induced b a…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice

et al. 2012

View full text Add to dashboard Cite

Aims/hypothesis Hyperlipidaemia is an independent risk factor for the progression of diabetic nephropathy, but its molecular mechanism remains elusive. We investigated in mice how diabetes and hyperlipidaemia cause renal lesions separately and in combination, and the involvement of Toll-like receptor 4 (TLR4) in the process. Methods Diabetes was induced in wild-type (WT) and Tlr4 knockout (KO) mice by intraperitoneal injection of streptozotocin (STZ). At 2 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Functional and histological analyses were carried out 6 weeks later. Results Compared with treatment with STZ or HFD alone, treatment of WT mice with both STZ and HFD markedly aggravated nephropathy, as indicated by an increase in albuminuria, mesangial expansion, infiltration of macrophages and upregulation of pro-inflammatory and extracellularmatrix-associated gene expression in glomeruli. In Tlr4 KO mice, the addition of an HFD to STZ had almost no effects on the variables measured. Production of protein S100 calcium binding protein A8 (calgranulin A; S100A8), a potent ligand for TLR4, was observed in abundance in macrophages infiltrating STZ-HFD WT glomeruli and in glomeruli of diabetic nephropathy patients. High-glucose and fatty acid treatment synergistically upregulated S100a8 gene expression in macrophages from WT mice, but not from KO mice. As putative downstream targets of TLR4, phosphorylation of interferon regulatory factor 3 (IRF3) was enhanced in kidneys of WT mice co-treated with STZ and HFD. Conclusions/interpretation Activation of S100A8/TLR4 signalling was elucidated in an animal model of diabetic glomerular injury accompanied with hyperlipidaemia, which may provide novel therapeutic targets in progressive diabetic nephropathy.

show abstract

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice

et al. 2012

View full text Add to dashboard Cite

show abstract

“…In the kidney, CD36 is expressed in the proximal tubule, collecting duct and loop of Henle with expression in the proximal tubule increased in diabetes [44]. Previous studies in cultured proximal tubule epithelial cells (PTECs) showed that CD36 activation leads to oxidative stress, apoptosis, and pro-fibrotic signalling (fibronectin expression, TGF-β release) [44–46]. Similarly, mice deficient in CD36 are resistant to renal fibrosis and oxidative stress in unilateral ureteral obstruction [46,47].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies in cultured proximal tubule epithelial cells (PTECs) showed that CD36 activation leads to oxidative stress, apoptosis, and pro-fibrotic signalling (fibronectin expression, TGF-β release) [44–46]. Similarly, mice deficient in CD36 are resistant to renal fibrosis and oxidative stress in unilateral ureteral obstruction [46,47]. Our data also support a role for CD36 in PTEC fibrogenesis through the stimulation of p38 MAPK and TGF-β receptor-mediated activation of Smad3, collagen type IV and fibronectin.…”

Section: Discussionmentioning

confidence: 99%

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Munkonda

Akbari

Landry

et al. 2018

J of Extracellular Vesicle

View full text Add to dashboard Cite

Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100–1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses. MPs were isolated from the media of differentiated, untreated human podocytes (hPODs) and administered to cultured human proximal tubule epithelial cells (PTECs). Treatment with podocyte MPs increased p38 and Smad3 phosphorylation and expression of the extracellular matrix (ECM) proteins fibronectin and collagen type IV. MP-induced responses were attenuated by co-treatment with the p38 inhibitor SB202190. A transforming growth factor beta (TGF-β) receptor inhibitor (LY2109761) blocked MP-induced Smad3 phosphorylation and ECM protein expression but not p38 phosphorylation suggesting that these responses occurred downstream of p38. Finally, blockade of the class B scavenger receptor CD36 completely abrogated MP-mediated p38 phosphorylation, downstream Smad3 activation and fibronectin/collagen type IV induction. Taken together our results suggest that podocyte MPs interact with proximal tubule cells and induce pro-fibrotic responses. Such interactions may contribute to the development of tubular fibrosis in glomerular disease.

show abstract

“…In addition to adrenomedullin, downregulation of the ␣ -synuclein (Snca) and CD36 genes, which may prevent excessive reactive oxygen species (ROS) production ( 34,35 ), was observed. The modulation of extracellular matrix components via the production of metalloproteinases is an important regulator of fat tissue remodeling.…”

Section: Gene Expression Analysis Of Stromal Vascular Cellsmentioning

confidence: 99%

A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations

Massiéra

Barbry

Guesnet

et al. 2010

Journal of Lipid Research

163

128

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org able to genetic factors as it has occurred relatively recently and is observed in a wide range of human populations. High-fat diets are considered to be obesogenic in that they produce a consistent increase in fat mass that is directly related to the content of the diet and duration of feeding. However, the contribution of dietary fats compared with an excess energy intake in increasing body weight remains controversial, as no major change in the total amount of ingested fats has occurred in the last two decades ( 1, 2 ).In addition to caloric excess, a qualitative issue has emerged as a risk factor for obesity in rodents and possibly in humans; i.e., the disequilibrium in polyunsaturated fatty acid (PUFA) metabolism with a high ratio of linoleic acid (C18:2 6, LA) versus ␣ -linolenic acid (C18:3 3, LNA) ( 3 ). Notably, in rodents, reducing this ratio from 59 to 2 under isolipidic, isoenergetic conditions (40% energy as fat) by inclusion of dietary LNA counteracted the enhancing effects of LA on body weight and fat mass, which then became similar to that observed with a chow diet ( 4 ).6 PUFAs were more potent than 3 PUFAs in promoting adipogenesis ( 5-7 ). When combined with high carbohydrate content, a linoleic acid-enriched diet was found to be pro-adipogenic in vivo through cAMP-dependent signaling ( 8 ). LA acts through arachidonic acid (C20:4 6, ARA) and prostacyclin, as pups from mice invalidated for the prostacyclin receptor (IP-R) and fed a LA-rich diet exhibit reduced body weight and fat mass compared with wild-type mice fed the same diet ( 4 ). Overall, these results emphasize the importance of adipose tissue development Abstract The prevalence of obesity has steadily increased over the last few decades. During this time, populations of industrialized countries have been exposed to diets rich in fat with a high content of linoleic acid and a low content of ␣ -linolenic acid compared with recommended intake. To assess the contribution of dietary fatty acids, male and female mice fed a high-fat diet (35% energy as fat, linoleic acid: ␣ -linolenic acid ratio of 28) were mated randomly and maintained after breeding on the same diet for successive generations. Offspring showed, over four generations, a gradual enhancement in fat mass due to combined hyperplasia and hypertrophy with no change in food intake. Transgenerational alterations in adipokine levels were accompa nied by hyperinsulinemia. Gene expression analyses of the stromal vascular fraction of adipose tissue, over generations, revealed discrete and steady changes in certain important players, such as CSF3 and Nocturnin. Thus, under conditions of genome stability and with no change in the regimen over four generations, we show that a Western-like fat diet induces a gradual fat mass enhancement, in accordance with the increasing prevalence of obesity observed in humans. -Massiera, F., P. Barbry, P. Guesnet, A. Joly, S. The prevalence of obesity and the risk of developing associated diseases ha...

show abstract

CD36 Regulates Oxidative Stress and Inflammation in Hypercholesterolemic CKD

Cited by 127 publications

References 51 publications

Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice

Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations

Contact Info

Product

Resources

About