Astragaloside IV inhibits palmitate-mediated oxidative stress and fibrosis in human glomerular mesangial cells via downregulation of CD36 expression

Su, Yong; Chen, Qingqing; Ma, Keke; Ju, Yinghui; Ji, Tianjiao; Wang, Zhongyuan; Li, Weizu

doi:10.1016/j.pharep.2018.12.008

Cited by 31 publications

(26 citation statements)

References 44 publications

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“…Indeed, lipotoxicity, in general, and exposure to NEFA, in particular, directly affect mesangial cell functions by activating the intrinsic apoptosis pathway, although the mechanisms of toxicity are not fully elucidated [113][114][115][116]. Furthermore, the use of fenofibrate (PPARα agonist) can prevent lipid-induced toxicity and oxidative stress in glomerular cells by inducing the expression of lipolytic enzymes [117].…”

Section: Lipotoxicity In Renal Cellsmentioning

confidence: 99%

“…Scavenger receptor A (SR-A) and class B-2 scavenger receptor (SR-B2), specifically CD36/FAT, are the main NEFA-uptake mediator in both physiological and pathophysiological situations [137]. These scavenger receptors are key elements in the fatty acid uptake, expressed in podocytes, mesangial cells, endothelial cells, and tubular cells, which is currently proposed as a potential therapeutic target in preclinical kidney disease [115,[138][139][140]. It has recently been described that the presence of advance oxidation protein products (AOPP) and hyperglycemia lead to CD36/FAT upregulation, as well as to increased CD36-dependent signaling through Wnt/β-catenin and PKC pathways, which is associated in the epithelial tubular cells with oxidative stress, inflammation, and fibrosis development [139,141,142].…”

Section: Lipotoxicity In Renal Cellsmentioning

confidence: 99%

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Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

Opazo-Ríos

Mas

Marín-Royo

et al. 2020

IJMS

189

147

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Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Serum lipid abnormalities and renal ectopic lipid accumulation have been associated with the development of kidney diseases, in particular diabetic nephropathy. Chronic hyperinsulinemia, often seen in type 2 diabetes, plays a crucial role in blood and liver lipid metabolism abnormalities, thus resulting in increased non-esterified fatty acids (NEFA). Excessive lipid accumulation alters cellular homeostasis and activates lipogenic and glycogenic cell-signaling pathways. Recent evidences indicate that both quantity and quality of lipids are involved in renal damage associated to lipotoxicity by activating inflammation, oxidative stress, mitochondrial dysfunction, and cell-death. The pathological effects of lipotoxicity have been observed in renal cells, thus promoting podocyte injury, tubular damage, mesangial proliferation, endothelial activation, and formation of macrophage-derived foam cells. Therefore, this review examines the recent preclinical and clinical research about the potentially harmful effects of lipids in the kidney, metabolic markers associated with these mechanisms, major signaling pathways affected, the causes of excessive lipid accumulation, and the types of lipids involved, as well as offers a comprehensive update of therapeutic strategies targeting lipotoxicity.

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Section: Lipotoxicity In Renal Cellsmentioning

confidence: 99%

Section: Lipotoxicity In Renal Cellsmentioning

confidence: 99%

Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

Opazo-Ríos

Mas

Marín-Royo

et al. 2020

IJMS

189

147

View full text Add to dashboard Cite

show abstract

“…CD36 is expressed in many kidney cells—podocytes, mesangial cells, proximal and distal tubular epithelium, microvascular endothelial cells, and interstitial macrophages [ 55 ]. This receptor plays a significant role in the progression of DN by (1) the initiation of renal lipid deposition [ 16 , 191 ] and (2) hyperglycemia or the interaction with products formed during chronic hyperglycemia, such as oxidized lipoproteins, AGEs, or AOPPs [ 172 , 176 , 183 , 192 ]. These cellular events promote inflammation, and oxidative and ER stress, resulting in kidney damage.…”

Section: The Role Of Cd36 In Diabetic Complicationsmentioning

confidence: 99%

“…Conditions such as hyperglycemia and dyslipidemia significantly change CD36 expression, its function, and its signaling pathways. The CD36-dependent mechanisms are important events in the pathogenesis of diabetic complications, such as nephropathy [ 14 , 15 , 16 , 17 ], retinopathy [ 18 , 19 , 20 ], neuropathy [ 21 , 22 ], and cardiomyopathy [ 23 , 24 , 25 , 26 ]. Importantly, CD36 disrupts the functions of organs in a tissue-specific manner by several different mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, CD36 disrupts the functions of organs in a tissue-specific manner by several different mechanisms. The abnormalities of carbohydrate and lipid metabolism correlate with changes to CD36 expression and subcellular localization [ 8 , 10 , 14 , 15 , 16 , 25 , 27 , 28 , 29 , 30 , 31 , 32 ] and contribute to an increase in uptake of fatty acids (FAs) and modified lipoproteins; intracellular accumulation of lipids such as triacylglycerols (TAGs), diacylglycerols (DAGs), and ceramides (CERs); and oxidative and endoplasmic reticulum (ER) stress—and thus activation of a number of signaling pathways that initiate inflammation, modulate insulin response and the utilization of energy substrates, and stimulate cell death and fibrosis leading to progressive, often irreversible organ dysfunction [ 5 , 7 , 9 , 10 , 11 , 14 , 15 , 16 , 18 , 19 , 22 , 23 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

Puchałowicz

Rać

2020

Cells

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CD36 is a multiligand receptor contributing to glucose and lipid metabolism, immune response, inflammation, thrombosis, and fibrosis. A wide range of tissue expression includes cells sensitive to metabolic abnormalities associated with metabolic syndrome and diabetes mellitus (DM), such as monocytes and macrophages, epithelial cells, adipocytes, hepatocytes, skeletal and cardiac myocytes, pancreatic β-cells, kidney glomeruli and tubules cells, pericytes and pigment epithelium cells of the retina, and Schwann cells. These features make CD36 an important component of the pathogenesis of DM and its complications, but also a promising target in the treatment of these disorders. The detrimental effects of CD36 signaling are mediated by the uptake of fatty acids and modified lipoproteins, deposition of lipids and their lipotoxicity, alterations in insulin response and the utilization of energy substrates, oxidative stress, inflammation, apoptosis, and fibrosis leading to the progressive, often irreversible organ dysfunction. This review summarizes the extensive knowledge of the contribution of CD36 to DM and its complications, including nephropathy, retinopathy, peripheral neuropathy, and cardiomyopathy.

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Astragaloside IV attenuates myocardial dysfunction in diabetic cardiomyopathy rats through downregulation of CD36‐mediated ferroptosis

Dong

et al. 2023

Phytotherapy Research

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Diabetic cardiomyopathy (DCM), one of the major complications of type 2 diabetes, is a leading cause of heart failure and death in advanced diabetes. Although there is an association between DCM and ferroptosis in cardiomyocytes, the internal mechanism of ferroptosis leading to DCM development remains unknown. CD36 is a key molecule in lipid metabolism that mediates ferroptosis. Astragaloside IV (AS-IV) confers various pharmacological effects such as antioxidant, anti-inflammatory, and immunomodulatory. In this study, we demonstrated that AS-IV was able to recover the dysfunction of DCM. In vivo experiments showed that AS-IV ameliorated myocardial injury and improved contractile function, attenuated lipid deposition, and decreased the expression level of CD36 and ferroptosis-related factors in DCM rats. In vitro experiments showed that AS-IV decreased CD36 expression and inhibited lipid accumulation and ferroptosis in PA-induced cardiomyocytes. The results demonstrated that AS-IV decreased cardiomyocyte injury and myocardial dysfunction by inhibiting ferroptosis mediated by CD36 in DCM rats. Therefore, AS-IV regulated the lipid metabolism of cardiomyocytes and inhibited cellular ferroptosis, which may have potential clinical value in DCM treatment.

show abstract

Astragaloside IV inhibits palmitate-mediated oxidative stress and fibrosis in human glomerular mesangial cells via downregulation of CD36 expression

Cited by 31 publications

References 44 publications

Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

Astragaloside IV attenuates myocardial dysfunction in diabetic cardiomyopathy rats through downregulation of CD36‐mediated ferroptosis

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