Serum integrative omics reveals the landscape of human diabetic kidney disease

Liu, Shijia; Gui, Yuan; Wang, Mark S.; Zhang, Lu; Xu, Tingting; Pan, Yuchen; Zhang, Ke; Yu, Ying; Lin, Xiao Jun; Qiao, Yi; Bonin, Christopher; Hargis, Geneva; Huan, Tao; Yu, Yonghao; Jiang, Tao; Zhang, Rong; Kreutzer, Donald L.; Zhou, Yanjiao; Tian, Xiao‐Jun; Wang, Yanlin; Fu, Haiyan; An, Xiaofei; Liu, Silvia; Zhou, Dong

doi:10.1016/j.molmet.2021.101367

Cited by 24 publications

(22 citation statements)

References 51 publications

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“…Urinary or serum proteomics for the study of DKD produced compelling results, [108][109][110] which could be conjugated with metabolomics for integrative analysis. For instance, Liu et al 104 concluded that the accuracy of DKD prediction could be improved by performing integrative serum proteomics and metabolomics data analysis Owens et al 111 aimed to develop a model for predicting progressive kidney damage based on a biomarker panel of serum creatinine, osteopontin, tryptase, urea and eGFR. Owens and collaborators obtained an accuracy of 84.3% in predicting future progressive chronic kidney disease at baseline, greater than eGFR (66.1%), sCr (67.7%), albuminuria (53.2%), or albumin-creatinine ratio (53.2%).…”

Section: Towards the Future: Multi-omics Analysis And Panels Of Bioma...mentioning

confidence: 99%

“…In support to these findings, Liu et al 103 also observed that increased urinary fumarate and malate predict of progressive DKD in patients with type 2 diabetes independently of eGFR and albuminuria, although urinary citrate levels were observed to be decreased. More recently, Liu et al 104 after analyzing the serum of 1513 individuals, with type 2 diabetes, with early‐stage and advanced‐stage DKD, and healthy controls, concluded that higher circulating levels of glycerol‐3‐galactoside were negatively associated with eGFR and could constitute a potential independent biomarker to predict early DKD. Since glycerol‐3‐galactoside is a metabolite of glycerolipid synthesis, this suggests that galactose and glycerolipid metabolism are likely disturbed in DKD.…”

Section: Metabolomics Applied To the Diagnosis And Prognosis Of Dkdmentioning

confidence: 99%

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Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Pereira

Carrageta

Oliveira

et al. 2022

Medicinal Research Reviews

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Diabetic kidney disease (DKD) is one of the most prevalent comorbidities of diabetes mellitus and the leading cause of the end‐stage renal disease (ESRD). DKD results from chronic exposure to hyperglycemia, leading to progressive alterations in kidney structure and function. The early development of DKD is clinically silent and when albuminuria is detected the lesions are often at advanced stages, leading to rapid kidney function decline towards ESRD. DKD progression can be arrested or substantially delayed if detected and addressed at early stages. A major limitation of current methods is the absence of albuminuria in non‐albuminuric phenotypes of diabetic nephropathy, which becomes increasingly prevalent and lacks focused therapy. Metabolomics is an ever‐evolving omics technology that enables the study of metabolites, downstream products of every biochemical event that occurs in an organism. Metabolomics disclosures complex metabolic networks and provide knowledge of the very foundation of several physiological or pathophysiological processes, ultimately leading to the identification of diseases' unique metabolic signatures. In this sense, metabolomics is a promising tool not only for the diagnosis but also for the identification of pre‐disease states which would confer a rapid and personalized clinical practice. Herein, the use of metabolomics as a tool to identify the DKD metabolic signature of tubule interstitial lesions to diagnose or predict the time‐course of DKD will be discussed. In addition, the proficiency and limitations of the currently available high‐throughput metabolomic techniques will be discussed.

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Section: Towards the Future: Multi-omics Analysis And Panels Of Bioma...mentioning

confidence: 99%

Section: Metabolomics Applied To the Diagnosis And Prognosis Of Dkdmentioning

confidence: 99%

Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Pereira

Carrageta

Oliveira

et al. 2022

Medicinal Research Reviews

View full text Add to dashboard Cite

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“…Metabolomics were performed on sera as previously described. 33 We identified 97 differentially expressed serum metabolites between HA and CKD patients (Figure 1c; Supplementary Table S5; Supplementary Figure S1d). Partial least squares (PLS) regression indicates that metabolite distribution patterns are different between HA and CKD patients (Figure 1d).…”

Section: Global Proteome and Metabolome Characterization After Ckdmentioning

confidence: 99%

“…Serum metabolomics was performed as we previously reported. 33 Participant demographic and clinical characteristics are in Supplementary Table S2.…”

Section: Human Serum Metabolomicsmentioning

confidence: 99%

Calponin 2 harnesses metabolic reprogramming to determine kidney fibrosis

Gui

Jiang

Wang

et al. 2023

Preprint

Self Cite

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In the fibrotic kidneys, the extent of a formed deleterious microenvironment is determined by cellular mechanical forces. This process requires metabolism for energy; however, how cellular mechanics and metabolism are connected remains unclear. Our proteomics revealed that actin filament binding and cell metabolism are the two most dysregulated events in the fibrotic kidneys. As a prominent actin stabilizer, Calponin 2 (CNN2) is predominantly expressed in fibroblasts and pericytes. CNN2 knockdown preserves kidney function and alleviates fibrosis. Global proteomics profiled that CNN2 knockdown enhanced the activities of the key rate-limiting enzymes and regulators of fatty acid oxidation (FAO) in diseased kidneys. Inhibiting carnitine palmitoyltransferase 1α in the FAO pathway results in lipid accumulation and extracellular matrix deposition in the fibrotic kidneys, which were restored after CNN2 knockdown. In patients, increased serum CNN2 levels are correlated with lipid content. Bioinformatics and chromatin immunoprecipitation showed that CNN2 interactor, estrogen receptor 2 (ESR2) binds peroxisome proliferator-activated receptor-α (PPARα) to transcriptionally regulate FAO downstream target genes expression amid kidney fibrosis. In vitro, ESR2 knockdown repressed the mRNA levels of PPARα and the key genes in the FAO pathway. Consequently, activation of PPARα reduced CNN2-induced matrix inductions. Our results suggest that balancing cell mechanics and metabolism is crucial to develop therapeutic strategies to halt kidney fibrosis.

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“…In recent years, metabolomics technology has become more and more widely used in clinical research, accounting for 95% of the global clinical trial workload ( Jacob et al, 2019 ). Using metabolomics technology to understand the changes of metabolites and metabolic pathways before and after the onset of the disease, to further understand the pathogenesis of the disease, it is possible to predict the progression of the disease, early diagnosis and improve the level of treatment ( Ishikawa et al, 2016 ; LeWitt et al, 2017 ; Peña-Bautista et al, 2019 ; Liu X. et al, 2020 ; Amerikanou et al, 2021 ; Liu S. et al, 2021 ). Goffredo et al measured a total of 180 plasma metabolites in 78 obese adolescents by a targeted metabolomics approach and found that obese NAFLD adolescents had higher plasma levels of isoleucine, valine, lysine and tryptophan.…”

Section: Metabolomics Applied To the Diagnosis Of Nafldmentioning

confidence: 99%

Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine

et al. 2022

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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world, and it often coexists with insulin resistance-related diseases including obesity, diabetes, hyperlipidemia, and hypertension, which seriously threatens human health. Better prevention and treatment strategies are required to improve the impact of NAFLD. Although needle biopsy is an effective tool for diagnosing NAFLD, this method is invasive and difficult to perform. Therefore, it is very important to develop more efficient approaches for the early diagnosis of NAFLD. Traditional Chinese medicine (TCM) can play a certain role in improving symptoms and protecting target organs, and its mechanism of action needs to be further studied. Metabolomics, the study of all metabolites that is thought to be most closely associated with the patients’ characters, can provide useful clinically biomarkers that can be applied to NAFLD and may open up new methods for diagnosis. Metabolomics technology is consistent with the overall concept of TCM, and it can also be used as a potential mechanism to explain the effects of TCM by measuring biomarkers by metabolomics. Based on PubMed/MEDLINE and other databases, this paper retrieved relevant literature NAFLD and TCM intervention in NAFLD using metabolomics technology in the past 5 years were searched, and the specific metabolites associated with the development of NAFLD and the potential mechanism of Chinese medicine on improving symptoms were summarized.

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Serum integrative omics reveals the landscape of human diabetic kidney disease

Cited by 24 publications

References 51 publications

Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Calponin 2 harnesses metabolic reprogramming to determine kidney fibrosis

Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine

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