Abstract | OBJECTIVE: METHODS: Peritoneal inflammation was induced in male Sprague-Dawley rats by intraperitoneal injections of 4.25% glucose dialysate (100 mg/kg body weight) daily for 4 weeks, with the addition of lipopolysaccharides (0.6 mg/kg body weight) on days 8, 10, 12, 22, 24, and 26. Peritoneal Smad7 gene transfer was achieved using an ultrasound microbubble mediated, doxycycline regulated, Smad7-expressing plasmid on day 0 and day 14 after initiation of PD. An empty vector was used as control. All rats were sacrificed after 4 weeks of PD. Peritoneal inflammatory response, including infiltration of total leukocytes (OX-1 positive) and macrophages (ED-1 positive) and expression of interleukin (IL)-1beta and tumor necrosis factor-alpha ( TNF-alpha), was examined by immunofluorescence and RT-PCR. RESULTS: After PD, peritoneal inflammation developed in control animals, as demonstrated by an increase in the number of OX-1-positive and ED-1-positive cells and upregulation of IL-1beta and TNF-alpha mRNA and protein expression. In contrast, in animals treated with Smad7 gene transfer, IL-1beta and TNF-alpha expression and OX-1-positive and ED-1-positive cell infiltration were significantly inhibited. Furthermore, prevention of peritoneal inflammation by overexpression of Smad7 was associated with inhibition of phosphorylation of Smad2/3, a downstream of the TGF-beta signaling pathway, as well as TGF-beta1 expression. CONCLUSION: Overexpression of Smad7 suppresses peritoneal inflammation induced by high glucose and lipopolysaccharides. The ability of Smad7 gene transfer to inhibit peritoneal inflammation indicates that targeting TGF-beta/Smad signaling may represent a new therapeutic strategy for the treatment of peritoneal complications associated with PD.
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Authors | Jing Nie, Wenke Hao, Xianrui Dou, Xin Wang, Ning Luo, Hui Y Lan, Xueqing Yu |
Journal | Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
(Perit Dial Int)
2007 Sep-Oct
Vol. 27
Issue 5
Pg. 580-8
ISSN: 0896-8608 [Print] United States |
PMID | 17704451
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Inflammation Mediators
- Lipopolysaccharides
- Smad7 Protein
- Smad7 protein, rat
- Transforming Growth Factor beta
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Topics |
- Animals
- Disease Models, Animal
- Gene Transfer Techniques
- Inflammation Mediators
(administration & dosage, metabolism, physiology)
- Lipopolysaccharides
(administration & dosage)
- Male
- Peritoneal Dialysis
- Peritonitis
(genetics, metabolism, pathology, prevention & control)
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(genetics)
- Smad7 Protein
(administration & dosage, biosynthesis, genetics)
- Transforming Growth Factor beta
(antagonists & inhibitors, biosynthesis, genetics)
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