DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules

Guanshi Zhang, Jialing Zhang, Rachel J. DeHoog, Subramaniam Pennathur, Christopher R. Anderton, Manjeri A. Venkatachalam, Theodore Alexandrov, Livia S. Eberlin, Kumar Sharma

Research output: Contribution to journalArticle

Abstract

Introduction: Diabetic kidney disease (DKD) is the most prevalent complication in diabetic patients, which contributes to high morbidity and mortality. Urine and plasma metabolomics studies have been demonstrated to provide valuable insights for DKD. However, limited information on spatial distributions of metabolites in kidney tissues have been reported. Objectives: In this work, we employed an ambient desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) coupled to a novel bioinformatics platform (METASPACE) to characterize the metabolome in a mouse model of DKD. Methods: DESI-MSI was performed for spatial untargeted metabolomics analysis in kidneys of mouse models (F1 C57BL/6J-Ins2Akita male mice at 17 weeks of age) of type 1 diabetes (T1D, n = 5) and heathy controls (n = 6). Results: Multivariate analyses (i.e., PCA and PLS-DA (a 2000 permutation test: P < 0.001)) showed clearly separated clusters for the two groups of mice on the basis of 878 measured m/z’s in kidney cortical tissues. Specifically, mice with T1D had increased relative abundances of pseudouridine, accumulation of free polyunsaturated fatty acids (PUFAs), and decreased relative abundances of cardiolipins in cortical proximal tubules when compared with healthy controls. Conclusion: Results from the current study support potential key roles of pseudouridine and cardiolipins for maintaining normal RNA structure and normal mitochondrial function, respectively, in cortical proximal tubules with DKD. DESI-MSI technology coupled with METASPACE could serve as powerful new tools to provide insight on fundamental pathways in DKD.

Original languageEnglish (US)
Article number11
JournalMetabolomics
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2020

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Electrospray ionization
Proximal Kidney Tubule
Electrospray Ionization Mass Spectrometry
Diabetic Nephropathies
Mitochondrial Membranes
Mass spectrometry
Desorption
Membranes
Lipids
Imaging techniques
Pseudouridine
Cardiolipins
Metabolomics
Kidney
Tissue
Passive Cutaneous Anaphylaxis
Metabolome
Diabetes Complications
Bioinformatics
Medical problems

Keywords

  • DESI-MSI
  • Diabetic kidney disease
  • Lipid metabolism
  • Renal proximal tubule

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules. / Zhang, Guanshi; Zhang, Jialing; DeHoog, Rachel J.; Pennathur, Subramaniam; Anderton, Christopher R.; Venkatachalam, Manjeri A.; Alexandrov, Theodore; Eberlin, Livia S.; Sharma, Kumar.

In: Metabolomics, Vol. 16, No. 1, 11, 01.01.2020.

Research output: Contribution to journalArticle

Zhang, Guanshi ; Zhang, Jialing ; DeHoog, Rachel J. ; Pennathur, Subramaniam ; Anderton, Christopher R. ; Venkatachalam, Manjeri A. ; Alexandrov, Theodore ; Eberlin, Livia S. ; Sharma, Kumar. / DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules. In: Metabolomics. 2020 ; Vol. 16, No. 1.
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abstract = "Introduction: Diabetic kidney disease (DKD) is the most prevalent complication in diabetic patients, which contributes to high morbidity and mortality. Urine and plasma metabolomics studies have been demonstrated to provide valuable insights for DKD. However, limited information on spatial distributions of metabolites in kidney tissues have been reported. Objectives: In this work, we employed an ambient desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) coupled to a novel bioinformatics platform (METASPACE) to characterize the metabolome in a mouse model of DKD. Methods: DESI-MSI was performed for spatial untargeted metabolomics analysis in kidneys of mouse models (F1 C57BL/6J-Ins2Akita male mice at 17 weeks of age) of type 1 diabetes (T1D, n = 5) and heathy controls (n = 6). Results: Multivariate analyses (i.e., PCA and PLS-DA (a 2000 permutation test: P < 0.001)) showed clearly separated clusters for the two groups of mice on the basis of 878 measured m/z’s in kidney cortical tissues. Specifically, mice with T1D had increased relative abundances of pseudouridine, accumulation of free polyunsaturated fatty acids (PUFAs), and decreased relative abundances of cardiolipins in cortical proximal tubules when compared with healthy controls. Conclusion: Results from the current study support potential key roles of pseudouridine and cardiolipins for maintaining normal RNA structure and normal mitochondrial function, respectively, in cortical proximal tubules with DKD. DESI-MSI technology coupled with METASPACE could serve as powerful new tools to provide insight on fundamental pathways in DKD.",
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T1 - DESI-MSI and METASPACE indicates lipid abnormalities and altered mitochondrial membrane components in diabetic renal proximal tubules

AU - Zhang, Guanshi

AU - Zhang, Jialing

AU - DeHoog, Rachel J.

AU - Pennathur, Subramaniam

AU - Anderton, Christopher R.

AU - Venkatachalam, Manjeri A.

AU - Alexandrov, Theodore

AU - Eberlin, Livia S.

AU - Sharma, Kumar

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Introduction: Diabetic kidney disease (DKD) is the most prevalent complication in diabetic patients, which contributes to high morbidity and mortality. Urine and plasma metabolomics studies have been demonstrated to provide valuable insights for DKD. However, limited information on spatial distributions of metabolites in kidney tissues have been reported. Objectives: In this work, we employed an ambient desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) coupled to a novel bioinformatics platform (METASPACE) to characterize the metabolome in a mouse model of DKD. Methods: DESI-MSI was performed for spatial untargeted metabolomics analysis in kidneys of mouse models (F1 C57BL/6J-Ins2Akita male mice at 17 weeks of age) of type 1 diabetes (T1D, n = 5) and heathy controls (n = 6). Results: Multivariate analyses (i.e., PCA and PLS-DA (a 2000 permutation test: P < 0.001)) showed clearly separated clusters for the two groups of mice on the basis of 878 measured m/z’s in kidney cortical tissues. Specifically, mice with T1D had increased relative abundances of pseudouridine, accumulation of free polyunsaturated fatty acids (PUFAs), and decreased relative abundances of cardiolipins in cortical proximal tubules when compared with healthy controls. Conclusion: Results from the current study support potential key roles of pseudouridine and cardiolipins for maintaining normal RNA structure and normal mitochondrial function, respectively, in cortical proximal tubules with DKD. DESI-MSI technology coupled with METASPACE could serve as powerful new tools to provide insight on fundamental pathways in DKD.

AB - Introduction: Diabetic kidney disease (DKD) is the most prevalent complication in diabetic patients, which contributes to high morbidity and mortality. Urine and plasma metabolomics studies have been demonstrated to provide valuable insights for DKD. However, limited information on spatial distributions of metabolites in kidney tissues have been reported. Objectives: In this work, we employed an ambient desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) coupled to a novel bioinformatics platform (METASPACE) to characterize the metabolome in a mouse model of DKD. Methods: DESI-MSI was performed for spatial untargeted metabolomics analysis in kidneys of mouse models (F1 C57BL/6J-Ins2Akita male mice at 17 weeks of age) of type 1 diabetes (T1D, n = 5) and heathy controls (n = 6). Results: Multivariate analyses (i.e., PCA and PLS-DA (a 2000 permutation test: P < 0.001)) showed clearly separated clusters for the two groups of mice on the basis of 878 measured m/z’s in kidney cortical tissues. Specifically, mice with T1D had increased relative abundances of pseudouridine, accumulation of free polyunsaturated fatty acids (PUFAs), and decreased relative abundances of cardiolipins in cortical proximal tubules when compared with healthy controls. Conclusion: Results from the current study support potential key roles of pseudouridine and cardiolipins for maintaining normal RNA structure and normal mitochondrial function, respectively, in cortical proximal tubules with DKD. DESI-MSI technology coupled with METASPACE could serve as powerful new tools to provide insight on fundamental pathways in DKD.

KW - DESI-MSI

KW - Diabetic kidney disease

KW - Lipid metabolism

KW - Renal proximal tubule

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