Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging

Autor: Lu Tian, Wanfang Li, Jinfeng Wei, Zhi Zhou, Yanhua Chen, Zhonghua Wang, Wenqing Fu, Yaqi Liu, Baili Wang, Bingshu He, Meiling Huo, Jianzhen Xia, Zeper Abliz
Jazyk: angličtina
Rok vydání: 2021
Předmět:
BUN
blood urea nitrogen
VIP
variable importance in projection
AGEs
advanced glycation end products
p-AMPK
phosphorylated adenosine monophosphate activated protein kinase
Diabetic nephropathy
PG
phosphatidylglycerol
UMP
uridine monophosphate
PC
phosphatidylcholine
GMP
guanosine monophosphate
0302 clinical medicine
DM
diabetes mellitus
GSH
glutathione
PA
phosphatidic acid
General Pharmacology
Toxicology and Pharmaceutics
PUFA
polyunsaturated fatty acids
LysoPG
lysophosphatidylglycerol
LysoPC
lysophosphatidylcholine
0303 health sciences
Kidney
TG
triglyceride
Chemistry
GLU
glucose
Metabolic reprogramming
AFADESI
air flow-assisted desorption electrospray ionization
PS
phosphatidylserine
MSI
mass spectrometry imaging
medicine.anatomical_structure
Biochemistry
030220 oncology & carcinogenesis
SDH
succinate dehydrogenase
Original Article
SGLTs
sodium-glucose cotransporters
TCHO
total cholesterol
medicine.drug
ATP
adenosine triphosphate
CL
cardiolipin
Spatial-resolved metabolomics
FBG
fasting blood glucose
DESI
desorption electrospray ionization
TCA
tricarboxylic acid
PPP
pentose phosphate pathway
HbA1c
glycosylated hemoglobin
RM1-950
AMPK
adenosine monophosphate activated protein kinase
Astragaloside IV
PE
phosphatidylethanolamine
STZ
streptozotocin
Mass spectrometry imaging
DN
diabetic nephropathy
03 medical and health sciences
ROS
reactive oxygen species
Metabolomics
ROI
regions of interest
medicine
Carnitine
NMR
nuclear magnetic resonance
DPA
docosapentaenoic acid
030304 developmental biology
Desorption electrospray ionization
Cre
creatinine
SM
sphingomyelin
medicine.disease
Streptozotocin
ESKD
end-stage kidney disease
Sphingolipid
ADP
adenosine diphosphate
MS
mass spectrometry
AMP
adenosine monophosphate
MALDI
matrix-assisted laser desorption ionization
HPLC
high-performance liquid chromatography
Na-CMC
sodium carboxymethyl cellulose
H&E
hematoxylin and eosin
Therapeutics. Pharmacology
DAG
diacylglycerol
AST
astragaloside IV
Zdroj: Acta Pharmaceutica Sinica B, Vol 11, Iss 11, Pp 3665-3677 (2021)
Acta Pharmaceutica Sinica. B
ISSN: 2211-3835
Popis: Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.
Graphical abstract The present study revealed region-specific metabolic reprogramming during diabetic nephropathy (DN) by using air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI).Image 1
Databáze: OpenAIRE
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