Proteome Analysis of Serum from Type 2 Diabetics with Nephropathy

Kim, Hyun Jung; Cho, Eun Hee; Yoo, Ji Hye; Kim, Pan Kyeom; Shin, Juyeon; Kim, Mi Ryung; Kim, Chan Wha

doi:10.1021/pr060489g

Cited by 79 publications

(60 citation statements)

References 51 publications

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“…Differential proteome expressions among the non-diabetic and STZ-induced groups at six and 24 weeks were analyzed by 2-DE and nano-LC-ESI-MS/MS. Among these identified proteins, we focused on Gpx3 and annexin A3 because a literature survey [25,26] suggested their potential as biomarkers for diagnosing DN, as well as the availability of readily available reagents such as antibodies.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of glomeruli from streptozotocin-induced diabetic rats

Kim¹,

Kwon²,

Kim³

et al. 2014

Biotechnol Bioproc E

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The kidney glomeruli are the sites of plasma filtration and production of primary urine. However, they are also the locus of kidney diseases, which progress to chronic renal failure. Glomeruli are a major target of injury in diabetic nephropathy (DN). The mechanisms by which glomerular filtration are regulated are poorly understood, and proteomic investigations of isolated glomeruli on the progressive development of DN in animal models have not been determined. To understand the molecular mechanism leading to DN, especially the glomerular injury mechanism, the differences in the glomerular proteomes of streptozotocin (STZ)-induced-and non-diabetic rats at six and 24 weeks were analyzed via two-dimensional electrophoresis (2-DE). To identify the progressive stages of DN, body weight, blood glucose, and proteinuria were measured periodically, and pathological changes were evaluated by periodic acid-Schiff staining. Magnetic beads were used to isolate glomeruli from kidneys and the glomerular proteomes of non-diabetic and STZ-induced diabetic rats were analyzed by 2-DE and nano-LC-ESI-MS/MS. Glutathione peroxidase 3, peroxiredoxin 2, and histone H2A were down-regulated, and annexin A3 was up-regulated, in the STZ-induced group compared with the controls. Glutathione peroxidase 3 and annexin A3, which might help elucidate the mechanism of DN, were verified by Western blotting. These proteins could potentially provide insight into the mechanism of glomerular injury in DN.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of glomeruli from streptozotocin-induced diabetic rats

Kim¹,

Kwon²,

Kim³

et al. 2014

Biotechnol Bioproc E

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“…One study found that subjects with type 1 diabetic nephropathy had an increased ApoE level (26). Another study used twodimensional electrophoresis to identify serum biomarkers for the diagnosis type 2 diabetic nephropathy and found that ApoE was a potential biomarker (27). The present study was the first large sample association study of lipids levels with type 2 diabetic nephropathy in Chinese, which included ApoE as one of the lipid metabolism parameters.…”

Section: Discussionmentioning

confidence: 71%

Circulating ApoE Level is Independently Associated with Urinary Albumin Excretion in Type 2 Diabetic Patients

Ling

et al. 2011

Intern. Med.

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Objective Evidence from many studies suggests that dyslipidemia has a pathogenetic role in the development and progression of diabetic nephropathy. The objective of this study was to evaluate the relationships between serum lipid parameters and urinary albumin excretion in type 2 diabetic patients from Shanghai, China. Methods A total of 1094 type 2 diabetic patients were recruited. The urinary albumin to creatinine ratio (ACR), serum total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), apolipoprotein A I (ApoA I), apolipoprotein B (ApoB), apolipoprotein E (ApoE) and lipoprotein (a) [Lp(a)] were measured and low density lipoprotein cholesterol (LDL-C) was calculated according to the Friedewald formula. An ACR of !30 μg/mg was defined as albuminuria, and <30 μg/mg as normoalbuminuria. Results The levels of ApoE and triglyceride were significantly higher in albuminuric group compared with normoalbuminuric group (p<0.001 and p=0.003, respectively). Differences of ACR among the groups based on the tertile of ApoE and the tertile of triglyceride were significant (both p<0.001). In a multiple linear regression model, ApoE was independently associated with ACR (β=0.003, 95%CI 0.002-0.005, p<0.001). Conclusion Serum ApoE level was independently associated with urinary albumin excretion in type 2 diabetic patients from Shanghai, China.

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“…Rac1/Cdc42 antibody with sequence similarities that recognized endogenous levels of total Rac1 and Cdc42 proteins were used in Western blots. Gel bands from Western blot were scanned with LAS, and analyzed using Multi Gauge image analysis software (Fuji Film) (Cho et al, 2007;Kim et al, 2007a).…”

Section: Western Blotting Analysismentioning

confidence: 99%

The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats

et al. 2012

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Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to kidney glomeruli. Podocytes are glomerular epithelial cells and play critical roles in the glomerular filtration barrier. Recent studies have shown the importance of regulating the podocyte actin cytoskeleton in early DN. The phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, simultaneously regulates Rac1 and Cdc42, which destabilize the podocyte actin cytoskeleton during early DN. In this study, in order to evaluate the reno-protective effects of wortmannin in early DN by regulating Rac1 and Cdc42, streptozotocin (STZ)-induced proteinuric renal disease (SPRD) rats were treated with wortmannin. The albuminuria value of the SPRD group was 3.55 ± 0.56 mg/day, whereas wortmannin group was 1.77 ± 0.48 mg/day. Also, the albumin to creatinine ratio (ACR) value of the SPRD group was 53.08 ± 10.82 mg/g, whereas wortmannin group was 20.27 ± 6.41 mg/g. Changes in the expression level of nephrin, podocin and Rac1/Cdc42, which is related to actin cytoskeleton in podocytes, by wortmannin administration were confirmed by Western blotting. The expression levels of nephrin (79.66 ± 0.02), podocin (87.81 ± 0.03) and Rac1/Cdc42 (86.12 ± 0.02) in the wortmannin group were higher than the expression levels of nephrin (55.32 ± 0.03), podocin (53.40 ± 0.06) and Rac1/Cdc42 (54.05 ± 0.04) in the SPRD group. In addition, expression and localization of nephrin, podocin and desmin were confirmed by immunofluorescence. In summary, we found for the first time that wortmannin has a reno-protective effect on SPRD rats during the early DN. The beneficial effects of wortmannin in SPRD rats indicate that this compound could be used to delay the progression of the disease during the early DN stage.

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Proteome Analysis of Serum from Type 2 Diabetics with Nephropathy

Cited by 79 publications

References 51 publications

Proteomic analysis of glomeruli from streptozotocin-induced diabetic rats

Proteomic analysis of glomeruli from streptozotocin-induced diabetic rats

Circulating ApoE Level is Independently Associated with Urinary Albumin Excretion in Type 2 Diabetic Patients

The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats

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