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Table 2 Role of urinary exosomal protein as biomarkers for DN

From: Role of exosomes in pathogenesis, diagnosis, and treatment of diabetic nephropathy

Protein

 

Level

Type of diabetes

Species

No. of participants case/(control)

Detection method of exosomal protein

Comparing groups

Disease condition

Ref

TF

Transferrin

↑

Type 2

Human

15 DM 3, 36 DM2, 74 DM 1, 19 HC

LC-MS/MS

Western blot

DKD (DM 3, DM 2) vs. DM 1 vs. HC

ACR> 30 mg/g

[77]

SERPINA1

Alpha-1 antitrypsin

↑

AFM

Afamin

↑

CTSD

Cathepsin D

↓

PHYHD1

Phytanoyl-CoA dioxygenase domain containing 1

↑

Type 2

Human

20 DN, 20 NDRD, 16 T2DM, 21 HC

DIA-MS data acquisition.

ELISA

DN vs. NDRD vs. T2DM vs. HC

Kidney biopsy

[78]

PAK6

Serine/threonine-protein kinase

Epidermal growth factor receptor

↑

↑

Type 2

Human

48/(48 T2DM, 48 HC)

LC-MS/MS

Western blot ELISA

DN vs. T2DM and HC

ACR> 30 mg/g;

eGFR < 60 ml/min/1.73m2

[79]

EGF

Epidermal growth factor receptor

↑

AMBP

MLL3

α-microglobulin/bikunin precursor

Histone-lysine N-methyltransferase

↑

↑

—–

Human

8/(8)

LC–MS/MS

SRM

DN vs. HC

ACR> 30 mg/g.

eGFR < 60 ml/min/1.73m2

[70]

MLL3

Histone-lysine N-methyltransferase

↑

VDAC1

Voltage-dependent anion-selective channel protein 1

↓

Regucalcin (SMP30)

Senescence marker protein-30

↓

Type 2

Rat Human

……….

Urine 4/(3)

Tissue 7/(4)

2-dimensional DIGE

Western blot, IHC, SRM

STZ-induced diabetic rat with renal fibrosis vs. HC

DN vs. HC

eGFR < 60 ml/min/1.73m2

Urine protein excretion of ≥ 150 mg/24 h

[80]

WT-1

Wilm’s tumor-1

↑

Type 1

Human

18/(30 DM, 25 HC)

WT1 detected in 19 out of 31

Western blot

Immunoblot

T1DM with proteinuria vs. T1DM without proteinuria and HC

T1DM

ACR> 30 mg/g.

Microalbumin >20 µg/min

[81]

[82]

PEPD

Xaa-Pro dipeptidase

↑

Type 2

Rat

7/(7)

nLC-ESI-MS/MS

Immunoblotting

ZDF rats sacrificed after 12 weeks, 20 weeks vs. lean control

 ......

[83]

MUP-1

Major Urinary Protein −1

↓

AQP5, AQP2

Aquaporins

↑

Type 2

Human

12 DN, 12 DM, 11 NDN, 7 HC

ELISA

Western blot

DN vs. DM vs. NDN vs. HC

Biopsy-proven

[84]

UMOD

Uromodulin

↑

Type 2

Human

22 Ma, 32 Mi, 46 No, 31 HC

ELISA

Ma vs. Mi vs. No vs. HC

ACR> 30 mg/g

[85]

CD 63

 

↓

—–

Human

8 Mi, 13 No

Flow cytometry

Mi vs. No

UAER from 30,300 mg/24 h

[86]

C-megalin

 

↑

Type 2

Human

19 Ma, 17 Mi, 20 No, 19 HC

Immunoblotting

Ma vs. Mi vs. No vs. HC

ACR> 30 mg/g

[87]

  1. HC Healthy control, DN diabetic nephropathy, DM diabetes mellitus, DKD diabetic kidney disease, ACR albumin to creatinine ratio, eGFR estimated glomerular filtration rate, AER albumin excretion rate, No normoalbuminuria, Mi microalbuminuria, Ma macroalbuminuria, SRM selected reaction monitoring, LC-MS/MS liquid chromatography-tandem mass spectrometry, DIGE two-dimensional difference gel electrophoresis, IHC immunohistochemistry, ZDF Zucker diabetic fatty rats, NDN non-diabetic nephropathy