Dataset Information

The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential.

ABSTRACT:

Objective

Although Smad3 has been considered as a downstream mediator of transforming growth factor-? (TGF-?) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear. The current study tests the hypothesis that Smad7 may play a protective role and has therapeutic potential for diabetic kidney disease.

Research design and methods

Protective role of Smad7 in diabetic kidney disease was examined in streptozotocin-induced diabetic mice that have Smad7 gene knockout (KO) and in diabetic rats given Smad7 gene transfer using an ultrasound-microbubble-mediated technique.

Results

We found that mice deficient for Smad7 developed more severe diabetic kidney injury than wild-type mice as evidenced by a significant increase in microalbuminuria, renal fibrosis (collagen I, IV, and fibronectin), and renal inflammation (interleukin-1? [IL-1?], tumor necrosis factor-? [TNF-?], monocyte chemoattractant protein-1 [MCP-1], intracellular adhesion molecule-1 [ICAM-1], and macrophages). Further studies revealed that enhanced renal fibrosis and inflammation in Smad7 KO mice with diabetes were associated with increased activation of both TGF-?/Smad2/3 and nuclear factor-?B (NF-?B) signaling pathways. To develop a therapeutic potential for diabetic kidney disease, Smad7 gene was transferred into the kidney in diabetic rats by an ultrasound-microbubble-mediated technique. Although overexpression of renal Smad7 had no effect on levels of blood glucose, it significantly attenuated the development of microalbuminuria, TGF-?/Smad3-mediated renal fibrosis such as collagen I and IV and fibronectin accumulation and NF-?B/p65-driven renal inflammation including IL-1?, TNF-?, MCP-1, and ICAM-1 expression and macrophage infiltration in diabetic rats.

Conclusions

Smad7 plays a protective role in diabetic renal injury. Overexpression of Smad7 may represent a novel therapy for the diabetic kidney complication.

SUBMITTER: Chen HY

PROVIDER: S-EPMC3028360 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential.

Chen Hai Yong HY Huang Xiao R XR Wang Wansheng W Li Jin Hua JH Heuchel Rainer L RL Chung Arthur C K AC Lan Hui Yao HY

Diabetes 20101027 2

<h4>Objective</h4>Although Smad3 has been considered as a downstream mediator of transforming growth factor-β (TGF-β) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear. The current study tests the hypothesis that Smad7 may play a protective role and has therapeutic potential for diabetic kidney disease.<h4>Research design and methods</h4>Protective role of Smad7 in diabetic kidney disease was examined in streptozotocin-induced diabetic mice that have Smad ...[more]

PMID: 20980457

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Dataset Information

The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential.

Objective

Research design and methods

Results

Conclusions

Publications

The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential.

Similar Datasets

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