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The gene transfer of soluble VEGF type I receptor (Flt-1) attenuates peritoneal fibrosis formation in mice but not soluble TGF- type II receptor gene transfer

¹Intestinal Diseases Research Programme and ²Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada; and ³Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan

Submitted 26 April 2004 ; accepted in final form 29 July 2004

Peritoneal fibrosis formation is a consequence of inflammation/injury and a significant medical problem to be solved. The effects of soluble VEGF receptor type I (sFlt-1) gene transfer on experimental peritoneal fibrosis were examined and compared with soluble transforming growth factor- (TGF-) receptor type II (sTGFRII) gene transfer. Male C57BL/6 mice were injected with 1.5 x 10⁸ plaque-forming unit of adenovirus encoding active TGF- (AdTGF) intraperitoneally. Some mice had been treated with sTGFRII or sFlt-1 plasmid injection into skeletal muscle with electroporation 4 days before virus administration. Mice were euthanized at day 14 after virus administration. AdTGF induced significant elevation of serum active TGF-, caused significant inflammatory response [weight loss, elevation of serum amyloid-P (SAP) and IL-12, increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA], and induced marked thickening of the peritoneum and collagen deposition. Gene transfer of sFlt-1 reduced the collagen deposition 81% in mesenteric tissue. Treatment with sFlt-1 decreased ICAM-1 and MCP-1 mRNA expression significantly. Significant negative correlation between serum sFlt-1 and placental growth factor level was observed, whereas there was no significant negative correlation between sFlt-1 and VEGF. On the other hand, sTGFRII treatment enhanced the AdTGF-induced inflammation (significant elevation of SAP, TNF-, and IL-12 levels and upregulation of ICAM-1 and MCP-1 mRNA expressions) and failed to prevent collagen deposition. These observations indicate that sFlt-1 gene transfer might be of therapeutic benefit in peritoneal fibrosis.

inflammation; adhesion; placental growth factor; monocyte chemoattractant protein-1; anti-inflammatory cytokine

This article has been cited by other articles:

				Y Motomura, W I Khan, R T El-Sharkawy, M Verma-Gandhu, E F Verdu, J Gauldie, and S M Collins Induction of a fibrogenic response in mouse colon by overexpression of monocyte chemoattractant protein 1 Gut, May 1, 2006; 55(5): 662 - 670. [Abstract] [Full Text] [PDF]