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Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice.

Wei T, Zhao L, Jia J, Xia H, Du Y, Lin Q, Lin X, Ye X, Yan Z, Gao H - Sci Rep (2015)

Bottom Line: Age-dependent and correlated metabolite analysis identified that cis-aconitate and allantoin could serve as biomarkers for the diagnosis of DN.Further correlative analysis revealed that the enzymes dimethylarginine dimethylaminohydrolase (DDAH), guanosine triphosphate cyclohydrolase I (GTPCH I), and 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) were involved in dimethylamine metabolism, ketogenesis and GTP metabolism pathways, respectively, and could be potential therapeutic targets for DN.Our results highlight that metabonomic analysis can be used as a tool to identify potential biomarkers and novel therapeutic targets to gain a better understanding of the mechanisms underlying the initiation and progression of diseases.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.

ABSTRACT
Diabetic nephropathy (DN) is one of the lethal manifestations of diabetic systemic microvascular disease. Elucidation of characteristic metabolic alterations during diabetic progression is critical to understand its pathogenesis and identify potential biomarkers and drug targets involved in the disease. In this study, (1)H nuclear magnetic resonance ((1)H NMR)-based metabonomics with correlative analysis was performed to study the characteristic metabolites, as well as the related pathways in urine and kidney samples of db/db diabetic mice, compared with age-matched wildtype mice. The time trajectory plot of db/db mice revealed alterations, in an age-dependent manner, in urinary metabolic profiles along with progression of renal damage and dysfunction. Age-dependent and correlated metabolite analysis identified that cis-aconitate and allantoin could serve as biomarkers for the diagnosis of DN. Further correlative analysis revealed that the enzymes dimethylarginine dimethylaminohydrolase (DDAH), guanosine triphosphate cyclohydrolase I (GTPCH I), and 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) were involved in dimethylamine metabolism, ketogenesis and GTP metabolism pathways, respectively, and could be potential therapeutic targets for DN. Our results highlight that metabonomic analysis can be used as a tool to identify potential biomarkers and novel therapeutic targets to gain a better understanding of the mechanisms underlying the initiation and progression of diseases.

No MeSH data available.


Related in: MedlinePlus

Histological examination of kidney tissues.Representative HE and PAS stains of kidney tissues from 17-week-old wildtype mice and db/db mice.
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f1: Histological examination of kidney tissues.Representative HE and PAS stains of kidney tissues from 17-week-old wildtype mice and db/db mice.

Mentions: Figure 1 shows representative images of the histological examination of hematoxylin-eosin (HE)-stained and periodic acid-schiff (PAS)-stained sections of kidneys from 17-week-old wildtype and db/db mice. HE staining results revealed prominent glomerular lesions in renal parenchyma at the late stage of DN in db/db mice. PAS-stained sections showed clear evidence of glomerulosclerosis. Diffuse mesangial matrix expansion and thickening of the glomerular capillary basement membranes observed in the kidney tissues of 17-week-old db/db mice are consistent with previous reports on chronic renal injury in diabetic animals12. These results indicated that at the age of 17 weeks the db/db mice develop clear manifestations of renal tissue damage and dysfunction.


Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice.

Wei T, Zhao L, Jia J, Xia H, Du Y, Lin Q, Lin X, Ye X, Yan Z, Gao H - Sci Rep (2015)

Histological examination of kidney tissues.Representative HE and PAS stains of kidney tissues from 17-week-old wildtype mice and db/db mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493693&req=5

f1: Histological examination of kidney tissues.Representative HE and PAS stains of kidney tissues from 17-week-old wildtype mice and db/db mice.
Mentions: Figure 1 shows representative images of the histological examination of hematoxylin-eosin (HE)-stained and periodic acid-schiff (PAS)-stained sections of kidneys from 17-week-old wildtype and db/db mice. HE staining results revealed prominent glomerular lesions in renal parenchyma at the late stage of DN in db/db mice. PAS-stained sections showed clear evidence of glomerulosclerosis. Diffuse mesangial matrix expansion and thickening of the glomerular capillary basement membranes observed in the kidney tissues of 17-week-old db/db mice are consistent with previous reports on chronic renal injury in diabetic animals12. These results indicated that at the age of 17 weeks the db/db mice develop clear manifestations of renal tissue damage and dysfunction.

Bottom Line: Age-dependent and correlated metabolite analysis identified that cis-aconitate and allantoin could serve as biomarkers for the diagnosis of DN.Further correlative analysis revealed that the enzymes dimethylarginine dimethylaminohydrolase (DDAH), guanosine triphosphate cyclohydrolase I (GTPCH I), and 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) were involved in dimethylamine metabolism, ketogenesis and GTP metabolism pathways, respectively, and could be potential therapeutic targets for DN.Our results highlight that metabonomic analysis can be used as a tool to identify potential biomarkers and novel therapeutic targets to gain a better understanding of the mechanisms underlying the initiation and progression of diseases.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035 China.

ABSTRACT
Diabetic nephropathy (DN) is one of the lethal manifestations of diabetic systemic microvascular disease. Elucidation of characteristic metabolic alterations during diabetic progression is critical to understand its pathogenesis and identify potential biomarkers and drug targets involved in the disease. In this study, (1)H nuclear magnetic resonance ((1)H NMR)-based metabonomics with correlative analysis was performed to study the characteristic metabolites, as well as the related pathways in urine and kidney samples of db/db diabetic mice, compared with age-matched wildtype mice. The time trajectory plot of db/db mice revealed alterations, in an age-dependent manner, in urinary metabolic profiles along with progression of renal damage and dysfunction. Age-dependent and correlated metabolite analysis identified that cis-aconitate and allantoin could serve as biomarkers for the diagnosis of DN. Further correlative analysis revealed that the enzymes dimethylarginine dimethylaminohydrolase (DDAH), guanosine triphosphate cyclohydrolase I (GTPCH I), and 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) were involved in dimethylamine metabolism, ketogenesis and GTP metabolism pathways, respectively, and could be potential therapeutic targets for DN. Our results highlight that metabonomic analysis can be used as a tool to identify potential biomarkers and novel therapeutic targets to gain a better understanding of the mechanisms underlying the initiation and progression of diseases.

No MeSH data available.


Related in: MedlinePlus