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Article: The protective role of Smad7 in diabetic kidney disease: Mechanism and therapeutic potential

TitleThe protective role of Smad7 in diabetic kidney disease: Mechanism and therapeutic potential
Authors
Issue Date2011
Citation
Diabetes, 2011, v. 60, n. 2, p. 590-601 How to Cite?
AbstractOBJECTIVE - 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. 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-1β [IL-1β], tumor necrosis factor-α [TNF-α], 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-β/Smad2/3 and nuclear factor-κB (NF-κB) 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-β/Smad3-mediated renal fibrosis such as collagen I and IV and fibronectin accumulation and NF-κB/p65-driven renal inflammation including IL-1β, TNF-α, 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. © 2011 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/200013
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, Hai-Yong-
dc.contributor.authorHuang, Xiaoru-
dc.contributor.authorWang, Wansheng-
dc.contributor.authorLi, Jinhua-
dc.contributor.authorHeuchel, Rainer Lothar-
dc.contributor.authorChung, Arthur Chi Kong-
dc.contributor.authorLan, Huiyao-
dc.date.accessioned2014-07-26T23:11:01Z-
dc.date.available2014-07-26T23:11:01Z-
dc.date.issued2011-
dc.identifier.citationDiabetes, 2011, v. 60, n. 2, p. 590-601-
dc.identifier.issn0012-1797-
dc.identifier.urihttp://hdl.handle.net/10722/200013-
dc.description.abstractOBJECTIVE - 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. 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-1β [IL-1β], tumor necrosis factor-α [TNF-α], 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-β/Smad2/3 and nuclear factor-κB (NF-κB) 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-β/Smad3-mediated renal fibrosis such as collagen I and IV and fibronectin accumulation and NF-κB/p65-driven renal inflammation including IL-1β, TNF-α, 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. © 2011 by the American Diabetes Association.-
dc.languageeng-
dc.relation.ispartofDiabetes-
dc.titleThe protective role of Smad7 in diabetic kidney disease: Mechanism and therapeutic potential-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.2337/db10-0403-
dc.identifier.pmid20980457-
dc.identifier.pmcidPMC3028360-
dc.identifier.scopuseid_2-s2.0-79551599216-
dc.identifier.volume60-
dc.identifier.issue2-
dc.identifier.spage590-
dc.identifier.epage601-
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000287172100029-

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