PMID- 20980457
OWN - NLM
STAT- MEDLINE
DCOM- 20110310
LR  - 20220321
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 60
IP  - 2
DP  - 2011 Feb
TI  - The protective role of Smad7 in diabetic kidney disease: mechanism and 
      therapeutic potential.
PG  - 590-601
LID - 10.2337/db10-0403 [doi]
AB  - OBJECTIVE: Although Smad3 has been considered as a downstream mediator of 
      transforming growth factor-beta (TGF-beta) 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-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha], 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-beta/Smad2/3 and nuclear factor-kappaB (NF-kappaB) 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-beta/Smad3-mediated renal fibrosis such as 
      collagen I and IV and fibronectin accumulation and NF-kappaB/p65-driven renal 
      inflammation including IL-1beta, TNF-alpha, 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.
FAU - Chen, Hai Yong
AU  - Chen HY
AD  - Department of Medicine and Therapeutics and Li Ka Shing Institute of Health 
      Sciences, The Chinese University of Hong Kong, Hong Kong, China.
FAU - Huang, Xiao R
AU  - Huang XR
FAU - Wang, Wansheng
AU  - Wang W
FAU - Li, Jin Hua
AU  - Li JH
FAU - Heuchel, Rainer L
AU  - Heuchel RL
FAU - Chung, Arthur C K
AU  - Chung AC
FAU - Lan, Hui Yao
AU  - Lan HY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101027
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (Smad7 Protein)
SB  - IM
MH  - Albuminuria/genetics/metabolism/pathology
MH  - Analysis of Variance
MH  - Animals
MH  - Blood Glucose
MH  - Blotting, Western
MH  - Cytokines/genetics/metabolism
MH  - Diabetes Mellitus, Experimental/genetics/*metabolism/pathology
MH  - Diabetic Nephropathies/genetics/*metabolism/pathology
MH  - Fibrosis/genetics/metabolism/pathology
MH  - Gene Transfer Techniques
MH  - Immunohistochemistry
MH  - Inflammation/genetics/metabolism/pathology
MH  - Kidney Glomerulus/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Smad7 Protein/genetics/*metabolism
PMC - PMC3028360
EDAT- 2010/10/29 06:00
MHDA- 2011/03/11 06:00
PMCR- 2012/02/01
CRDT- 2010/10/29 06:00
PHST- 2010/10/29 06:00 [entrez]
PHST- 2010/10/29 06:00 [pubmed]
PHST- 2011/03/11 06:00 [medline]
PHST- 2012/02/01 00:00 [pmc-release]
AID - db10-0403 [pii]
AID - 0403 [pii]
AID - 10.2337/db10-0403 [doi]
PST - ppublish
SO  - Diabetes. 2011 Feb;60(2):590-601. doi: 10.2337/db10-0403. Epub 2010 Oct 27.