scholarly journals Caveolin-1 Regulates Cellular Metabolism: A Potential Therapeutic Target in Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Shilu Luo ◽  
Ming Yang ◽  
Hao Zhao ◽  
Yachun Han ◽  
Na Jiang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Kidney Disease ◽  
Stress Responses ◽  
Therapeutic Target ◽  
Kidney Diseases ◽  
Cellular Metabolism ◽  
Metabolic Reprogramming ◽  
Potential Therapeutic Target ◽  
Caveolin 1 ◽  
Main Component

The kidney is an energy-consuming organ, and cellular metabolism plays an indispensable role in kidney-related diseases. Caveolin-1 (Cav-1), a multifunctional membrane protein, is the main component of caveolae on the plasma membrane. Caveolae are represented by tiny invaginations that are abundant on the plasma membrane and that serve as a platform to regulate cellular endocytosis, stress responses, and signal transduction. However, caveolae have received increasing attention as a metabolic platform that mediates the endocytosis of albumin, cholesterol, and glucose, participates in cellular metabolic reprogramming and is involved in the progression of kidney disease. It is worth noting that caveolae mainly depend on Cav-1 to perform the abovementioned cellular functions. Furthermore, the mechanism by which Cav-1 regulates cellular metabolism and participates in the pathophysiology of kidney diseases has not been completely elucidated. In this review, we introduce the structure and function of Cav-1 and its functions in regulating cellular metabolism, autophagy, and oxidative stress, focusing on the relationship between Cav-1 in cellular metabolism and kidney disease; in addition, Cav-1 that serves as a potential therapeutic target for treatment of kidney disease is also described.

scholarly journals Plasma membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer

2012 ◽  
Vol 132 (2) ◽  
pp. 472-484 ◽  
Author(s):  
Takuhei Yokoyama ◽  
Takayuki Enomoto ◽  
Satoshi Serada ◽  
Akiko Morimoto ◽  
Shinya Matsuzaki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endometrial Cancer ◽  
Plasma Membrane ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Membrane Proteomics

scholarly journals Connexin‐mediated cell communication in the kidney: A potential therapeutic target for future intervention of diabetic kidney disease?

2020 ◽  
Vol 105 (2) ◽  
pp. 219-229 ◽  
Author(s):  
Gareth W. Price ◽  
Joe A. Potter ◽  
Bethany M. Williams ◽  
Chelsy L. Cliff ◽  
Paul E. Squires ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Therapeutic Target ◽  
Diabetic Kidney Disease ◽  
Cell Communication ◽  
Potential Therapeutic Target ◽  
Diabetic Kidney

scholarly journals Histone Methyltransferase EZH2: A Potential Therapeutic Target for Kidney Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Li ◽  
Chao Yu ◽  
Shougang Zhuang
Keyword(s):  
Animal Models ◽  
Therapeutic Target ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Disease Model ◽  
Kidney Injury ◽  
Potential Therapeutic Target ◽  
Over Expression ◽  
Ezh2 Expression

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme that catalyzes the addition of methyl groups to histone H3 at lysine 27, leading to gene silencing. Mutation or over-expression of EZH2 has been linked to many cancers including renal carcinoma. Recent studies have shown that EZH2 expression and activity are also increased in several animal models of kidney injury, such as acute kidney injury (AKI), renal fibrosis, diabetic nephropathy, lupus nephritis (LN), and renal transplantation rejection. The pharmacological and/or genetic inhibition of EZH2 can alleviate AKI, renal fibrosis, and LN, but potentiate podocyte injury in animal models, suggesting that the functional role of EZH2 varies with renal cell type and disease model. In this article, we summarize the role of EZH2 in the pathology of renal injury and relevant mechanisms and highlight EZH2 as a potential therapeutic target for kidney diseases.

Gut microbiota and probiotics intervention: A potential therapeutic target for management of cardiometabolic disorders and chronic kidney disease?

2018 ◽  
Vol 130 ◽  
pp. 152-163 ◽  
Author(s):  
Marinaldo Pacífico Cavalcanti Neto ◽  
Jailane de Souza Aquino ◽  
Larissa de Fátima Romão da Silva ◽  
Ruanniere de Oliveira Silva ◽  
Keyth Sulamitta de Lima Guimarães ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Cardiometabolic Disorders

SO049HYPOXIA INDUCIBLE FACTOR-PROLYL HYDROXYLASE (HIF-PH) INHIBITION COUNTERACTS THE RENAL ENERGY METABOLISM ALTERATIONS IN THE EARLY STAGES OF DIABETIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sho Hasegawa ◽  
Tetsuhiro Tanaka ◽  
Tomoyuki Saito ◽  
Kenji Fukui ◽  
Takeshi Wakashima ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Urinary Albumin Excretion ◽  
Kidney Diseases ◽  
Tca Cycle ◽  
Renal Tissue ◽  
Metabolic Reprogramming ◽  
Normal Food ◽  
Renal Energy Metabolism

Abstract Background and Aims Hypoxia inducible factor (HIF)-prolyl hydroxylase (PH) inhibitors (also known as HIF stabilizers) increase endogenous erythropoietin production and serve as novel therapeutic agents against anemia in chronic kidney disease. Considering that HIF induces the expression of various genes, HIF stabilizers might have pleiotropic effects on the progression of kidney diseases as well as improvement in anemia. Interestingly, HIF induces the metabolic reprogramming from tricarboxylic acid (TCA) cycle to glycolysis as an adaptive response to hypoxia. However, it remains obscure how the metabolic reprogramming in renal tissue by HIF stabilization affects the pathophysiology of kidney diseases. Previous studies have shown accumulation of glucose and TCA cycle metabolites in diabetic renal tissue, which might be related to the progression of diabetic kidney disease (DKD). We hypothesized that HIF stabilization might reverse these metabolism alterations and conducted a proof-of-concept study using enarodustat (JTZ-951), an oral HIF-PH inhibitor. Method We utilized the streptozotocin-induced diabetic rat and alloxan-induced diabetic mouse models. Animals were divided into three groups: Control (normal animals eating normal food), DKD (diabetic animals eating normal food) and DKD+enarodustat (diabetic animals eating food mixed with enarodustat). Blood, urine and kidney samples were collected two weeks after grouping. Metabolism status in renal tissue were compared between groups from transcriptome and metabolome perspectives. Results Although plasma creatinine levels were not different between groups, enarodustat tended to reverse diabetic renal changes such as urinary albumin excretion, glomerulomegaly and glomerular basement membrane thickening (Figure 1). Transcriptome analysis has revealed that enarodustat counteracts the diabetic renal metabolism alterations; fatty acid and amino acid metabolisms were upregulated in diabetic renal tissue and downregulated by enarodustat, while glucose metabolism was upregulated by enarodustat. These symmetric metabolism alterations were confirmed by metabolome analysis (Figure 2); glycolysis and TCA cycle metabolites were accumulated, and amino acids were reduced in diabetic renal tissue, while these metabolism alterations were mitigated by enarodustat. Moreover, enarodustat alleviated the accumulation of glutathione disulfide (GSSG) in diabetic renal tissue and thus showed higher glutathione (GSH)/GSSG ratio, which suggested that enarodustat relieved oxidative stress in DKD. Conclusion HIF stabilization counteracts the renal energy metabolism alterations in the early stages of DKD, in association with the improvement in urinary albumin excretion and renal pathological abnormalities. Our study suggests that HIF stabilization may serve as a potential intervention targeting dysregulated energy metabolism of diabetic kidneys.

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