The link between phenotype and fatty acid metabolism in advanced chronic kidney disease

Chen, Dan-Qian; Chen, Hua; Lin, Changyong; Vaziri, Nosratola D.; Wang, Ming; Li, Xiang-Ri; Zhao, Ying-Yong

doi:10.1093/ndt/gfw415

Cited by 97 publications

(60 citation statements)

References 47 publications

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“…The total protein concentration was determined using Pierce™ BCA Protein Assay Kit (23227, Thermo Scientific, USA) according to the manufacturer's instructions. Protein expression was performed by Western blot analyses as described previously [17], [18]. The ratio of each protein was calculated by densitometry using free ImageJ software (version 1.48 v, NIH, Bethesda, MD, USA) and Band densities were normalized by Histone H3 or GAPDH expression levels.…”

Section: Methodsmentioning

confidence: 99%

“…Despite being relatively silent in normal adult kidneys, Wnt/β-catenin signaling is activated in the different CKD, such as obstructive nephropathy, adriamycin nephropathy, chronic allograft nephropathy and diabetic nephropathy [13], [14], [15], [16], which was accompanied by oxidative stress and inflammation. It was reported that activated oxidative stress and inflammation were closed associated with dysregulation of amino acid, uremic toxin (indoxyl sulfate, uric acid), bile acid, fatty acid, triglyceride, glycerophospholipid metabolisms in rats with chronic kidney disease [17], [18].…”

Section: Introductionmentioning

confidence: 99%

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Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease

et al. 2017

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Changes in plasma concentration of small organic metabolites could be due to their altered production or urinary excretion and changes in their urine concentration may be due to the changes in their filtered load, tubular reabsorption, and/or altered urine volume. Therefore, these factors should be considered in interpretation of the changes observed in plasma or urine of the target metabolite(s). Fasting plasma and urine samples from 180 CKD patients and 120 age-matched healthy controls were determined by UPLC-HDMS-metabolomics and quantitative real-time RT-PCR techniques. Compared with healthy controls, patients with CKD showed activation of NF-κB and up-regulation of pro-inflammatory and pro-oxidant mRNA and protein expression as well as down-regulation of Nrf2-associated anti-oxidant gene mRNA and protein expression, accompanied by activated canonical Wnt/β-catenin signaling. 124 plasma and 128 urine metabolites were identified and 40 metabolites were significantly altered in both plasma and urine. Plasma concentration and urine excretion of 25 metabolites were distinctly different between CKD and controls. They were related to amino acid, methylamine, purine and lipid metabolisms. Logistic regression identified four plasma and five urine metabolites. Parts of them were good correlated with eGFR or serum creatinine. 5-Methoxytryptophan and homocystine and citrulline were good correlated with both eGFR and creatinine. Clinical factors were incorporated to establish predictive models. The enhanced metabolite model showed 5-methoxytryptophan, homocystine and citrulline have satisfactory accuracy, sensitivity and specificity for predictive CKD. The dysregulation of CKD was related to amino acid, methylamine, purine and lipid metabolisms. 5-methoxytryptophan, homocystine and citrulline could be considered as additional GFR-associated biomarker candidates and for indicating advanced renal injury. CKD caused dysregulation of the plasma and urine metabolome, activation of inflammatory/oxidative pathway and Wnt/β-catenin signaling and suppression of antioxidant pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease

et al. 2017

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“…Fibrosis is a wound-healing response to either acute or chronic cellular injury that is characterized by the accumulation of extracellular matrix (ECM). Excessive evidence demonstrated that fibrogenesis is associated with renin-angiotensin system, inflammation and oxidative stress, transforming growth factor β (TGF-β)/Smad signaling, Wnt/βcatenin signaling and lipid metabolism [1][2][3][4][5][6][7][8][9][10]. Among them, TGF-β/ Smad signaling plays an important role in fibrosis [1,[11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

New insights into TGF-β/Smad signaling in tissue fibrosis

Chen

Wang

et al. 2018

Chemico-Biological Interactions

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Transforming growth factor-β1 (TGF-β1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic (Smad) signaling. Different TGF-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. This review presents an overview of the molecular mechanisms of TGF-β/Smad signaling pathway in renal, hepatic, pulmonary and cardiac fibrosis, followed by an in-depth discussion of their molecular mechanisms of intervention effects both in vitro and in vivo. The role of TGF-β/Smad signaling pathway in tumor or cancer is also discussed. Additionally, the current advances also highlight targeting TGF-β/Smad signaling pathway for the prevention of tissue fibrosis. The review reveals comprehensive pathophysiological mechanisms of tissue fibrosis. Particular challenges are presented and placed within the context of future applications against tissue fibrosis.

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“…Renal fibrosis is closely associated with mounting mediators and signaling pathways, such as oxidative stress, inflammation, microRNAs, transforming growth factor β1 (TGF-β1)/Smad and Wnt/β-catenin (Fig. 2), as well as the dysregulated uremic toxins, amino acids and lipid metabolism [92][93][94][95][96][97][98][99][100]. In recent decades, natural small molecules have gradually become an important therapeutic strategy for the prevention and treatment of renal fibrosis worldwide [22,101,102].…”

Section: Renal Disease and Fibrosismentioning

confidence: 99%

Natural products against renin-angiotensin system for antifibrosis therapy

Yang

Chen

Liu

et al. 2019

European Journal of Medicinal Chemistry

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The link between phenotype and fatty acid metabolism in advanced chronic kidney disease

Abstract: Advanced CKD in rats with adenine-induced chronic interstitial nephropathy results in profound changes in the serum metabolome, activation of inflammatory, oxidative and fibrotic pathways, and suppression of cytoprotective and antioxidant pathways.

Cited by 97 publications

References 47 publications

Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease

Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease

New insights into TGF-β/Smad signaling in tissue fibrosis

Natural products against renin-angiotensin system for antifibrosis therapy

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