General Information:

Id: 2,071
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Nephropathy, diabetic
Mus musculus
male
diabetic db/db mouse
article
Reference: Shibuya K et al.(2005) N-acetyl-seryl-aspartyl-lysyl-proline prevents renal insufficiency and mesangial matrix expansion in diabetic db/db mice. Diabetes 54: 838-845 [PMID: 15734863]

Interaction Information:

Comment The mesangial matrix expansion was increased more than twofold in db/db compared with db/m mice. Treatment with Ac-SDKP decreased the mesangial matrix area in a dose-dependent manner. There was a significant correlation between the mesangial matrix area and the plasma Ac-SDKP level.
Formal Description
Interaction-ID: 16697

gene/protein

AcSDKP

decreases_quantity of

tissue/cell line

mesangial matrix

in kidney
Comment Consistent with the results for mesangial matrix expansion, the diabetic db/db mice demonstrated overexpression of fibronectin and type IV collagen as compared with db/m mice. Administration of Ac-SDKP reduced the overexpression of fibronectin and type IV collagen in the glomeruli of db/db mice.
Formal Description
Interaction-ID: 16698

organism model

db/db mouse

increases_expression of

gene/protein

FN1

in kidney
Comment Consistent with the results for mesangial matrix expansion, the diabetic db/db mice demonstrated overexpression of fibronectin and type IV collagen as compared with db/m mice. Administration of Ac-SDKP reduced the overexpression of fibronectin and type IV collagen in the glomeruli of db/db mice.
Formal Description
Interaction-ID: 16699

organism model

db/db mouse

increases_expression of

gene/protein

COL4A

in kidney
Comment Consistent with the results for mesangial matrix expansion, the diabetic db/db mice demonstrated overexpression of fibronectin and type IV collagen as compared with db/m mice. Administration of Ac-SDKP reduced the overexpression of fibronectin and type IV collagen in the glomeruli of db/db mice.
Formal Description
Interaction-ID: 16700

gene/protein

AcSDKP

decreases_expression of

gene/protein

FN1

in kidney; in db/db mice
Comment Consistent with the results for mesangial matrix expansion, the diabetic db/db mice demonstrated overexpression of fibronectin and type IV collagen as compared with db/m mice. Administration of Ac-SDKP reduced the overexpression of fibronectin and type IV collagen in the glomeruli of db/db mice.
Formal Description
Interaction-ID: 16701

gene/protein

AcSDKP

decreases_expression of

gene/protein

COL4A

in kidney
Comment The plasma creatinine levels were higher in db/db than in db/m mice, but the treatment with Ac-SDKP normalized the elevation.
Formal Description
Interaction-ID: 16702

organism model

db/db mouse

increases_activity of

in blood
Comment The plasma creatinine levels were higher in db/db than in db/m mice, but the treatment with Ac-SDKP normalized the elevation.
Formal Description
Interaction-ID: 16703

gene/protein

AcSDKP

decreases_activity of

in blood; in db/db mice
Comment The urinary albumin excretion of the BSS-treated db/db mice was about 10-fold that of the db/m mice. The urinary albumin excretion in the Ac-SDKP-treated db/db mice was somewhat decreased compared with that in the BSS-treated db/db mice, but the difference was not statistically significant.
Formal Description
Interaction-ID: 16704

organism model

db/db mouse

increases_activity of

phenotype

albuminuria

Comment The urinary albumin excretion of the BSS-treated db/db mice was about 10-fold that of the db/m mice. The urinary albumin excretion in the Ac-SDKP-treated db/db mice was somewhat decreased compared with that in the BSS-treated db/db mice, but the difference was not statistically significant.
Formal Description
Interaction-ID: 16705

gene/protein

AcSDKP

NOT affects_activity of

phenotype

albuminuria

in db/db mice
Comment The nuclear translocation of Smad3 in glomeruli of the outer cortex was increased in db/db mice, the nuclear translocation of Smad3 was inhibited by Ac-SDKP. Ac-SDKP inhibited TGF-beta/Smad signaling in vivo.
Formal Description
Interaction-ID: 16706

organism model

db/db mouse

increases_transport of

gene/protein

SMAD3

into the nucleus
Comment The nuclear translocation of Smad3 in glomeruli of the outer cortex was increased in db/db mice, the nuclear translocation of Smad3 was inhibited by Ac-SDKP. Ac-SDKP inhibited TGF-beta/Smad signaling in vivo.
Formal Description
Interaction-ID: 16707

gene/protein

AcSDKP

decreases transport of

gene/protein

SMAD3

into the nucleus; in db/db mice
Comment The nuclear translocation of Smad3 in glomeruli of the outer cortex was increased in db/db mice, the nuclear translocation of Smad3 was inhibited by Ac-SDKP. Ac-SDKP inhibited TGF-beta/Smad signaling in vivo.
Formal Description
Interaction-ID: 16708

gene/protein

AcSDKP

decreases_activity of

in db/db mice
Comment The renal expression of TGF-beta1 was increased in db/db mice compared with db/m mice, the treatment with Ac-SDKP did not change the expression of TGF-beta1 in db/db mice.
Formal Description
Interaction-ID: 16709

organism model

db/db mouse

increases_expression of

gene/protein

TGFB1

in kidney
Drugbank entries Show/Hide entries for TGFB1
Comment The renal expression of TGF-beta1 was increased in db/db mice compared with db/m mice, the treatment with Ac-SDKP did not change the expression of TGF-beta1 in db/db mice.
Formal Description
Interaction-ID: 16710

gene/protein

AcSDKP

NOT affects_expression of

gene/protein

TGFB1

in kidney; in db/db mice
Drugbank entries Show/Hide entries for TGFB1
Comment The expression of TGF-beta type II receptor was upregulated in db/db mice, and the treatment with Ac-SDKP inhibited the expression in db/db mice.
Formal Description
Interaction-ID: 16711

organism model

db/db mouse

increases_expression of

gene/protein

TGFBR2

in kidney
Drugbank entries Show/Hide entries for TGFBR2
Comment The expression of TGF-beta type II receptor was upregulated in db/db mice, and the treatment with Ac-SDKP inhibited the expression in db/db mice.
Formal Description
Interaction-ID: 16712

gene/protein

AcSDKP

decreases_expression of

gene/protein

TGFBR2

in kidney; in db/db mice
Drugbank entries Show/Hide entries for TGFBR2
Comment Long-term Ac-SDKP treatment ameliorates renal insufficiency and glomerulosclerosis in db/db mice via inhibition of TGF-beta/Smad pathway, suggesting that Ac-SDKP could be useful in the treatment of diabetic nephropathy.
Formal Description
Interaction-ID: 16713

gene/protein

AcSDKP

decreases_activity of

phenotype

glomerulosclerosis

in db/db mice
Comment Long-term Ac-SDKP treatment ameliorates renal insufficiency and glomerulosclerosis in db/db mice via inhibition of TGF-beta/Smad pathway, suggesting that Ac-SDKP could be useful in the treatment of diabetic nephropathy.
Formal Description
Interaction-ID: 16714

gene/protein

AcSDKP

affects_activity of

disease

Nephropathy, diabetic